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Mitochondrial Quality and Quantity Control: Mitophagy Is a Potential Therapeutic Target for Ischemic Stroke

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Abstract

Ischemic stroke is a cerebrovascular disease with high mortality and disability, which seriously affects the health and lives of people around the world. Effective treatment for ischemic stroke has been limited by its complex pathological mechanisms. Increasing evidence has indicated that mitochondrial dysfunction plays an essential role in the occurrence, development, and pathological processes of ischemic stroke. Therefore, strict control of the quality and quantity of mitochondria via mitochondrial fission and fusion as well as mitophagy is beneficial to the survival and normal function maintenance of neurons. Under certain circumstances, excessive mitophagy also could induce cell death. This review discusses the dynamic changes and double-edged roles of mitochondria and related signaling pathways of mitophagy in the pathophysiology of ischemic stroke. Furthermore, we focus on the possibility of modulating mitophagy as a potential therapy for the prevention and prognosis of ischemic stroke. Notably, we reviewed recent advances in the studies of natural compounds, which could modulate mitophagy and exhibit neuroprotective effects, and discussed their potential application in the treatment of ischemic stroke.

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References

  1. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW et al (2021) Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation 143(8):e254–e743. https://doi.org/10.1161/CIR.0000000000000950

    Article  PubMed  Google Scholar 

  2. Deb P, Sharma S, Hassan KM (2010) Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 17(3):197–218. https://doi.org/10.1016/j.pathophys.2009.12.001

    Article  CAS  PubMed  Google Scholar 

  3. Adibhatla RM, Hatcher JF (2008) Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies. CNS Neurol Disord Drug Targets 7(3):243–253. https://doi.org/10.2174/187152708784936608

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Henninger N, Fisher M (2016) Extending the time window for endovascular and pharmacological reperfusion. Transl Stroke Res 7(4):284–293. https://doi.org/10.1007/s12975-015-0444-4

    Article  CAS  PubMed  Google Scholar 

  5. Aronowski J, Strong R, Grotta JC (1997) Reperfusion injury: demonstration of brain damage produced by reperfusion after transient focal ischemia in rats. J Cereb Blood Flow Metab 17(10):1048–1056. https://doi.org/10.1097/00004647-199710000-00006

    Article  CAS  PubMed  Google Scholar 

  6. Wang X, Asahi M, Lo EH (1999) Tissue type plasminogen activator amplifies hemoglobin-induced neurotoxicity in rat neuronal cultures. Neurosci Lett 274(2):79–82. https://doi.org/10.1016/s0304-3940(99)00682-5

    Article  CAS  PubMed  Google Scholar 

  7. Martin JL, Gruszczyk AV, Beach TE, Murphy MP, Saeb-Parsy K (2019) Mitochondrial mechanisms and therapeutics in ischaemia reperfusion injury. Pediatr Nephrol 34(7):1167–1174. https://doi.org/10.1007/s00467-018-3984-5

    Article  PubMed  Google Scholar 

  8. Yue R, Xia X, Jiang J, Yang D, Han Y, Chen X et al (2015) Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene. J Cell Physiol 230(9):2128–2141. https://doi.org/10.1002/jcp.24941

    Article  CAS  PubMed  Google Scholar 

  9. He Z, Ning N, Zhou Q, Khoshnam SE, Farzaneh M (2020) Mitochondria as a therapeutic target for ischemic stroke. Free Radic Biol Med 146:45–58. https://doi.org/10.1016/j.freeradbiomed.2019.11.005

    Article  CAS  PubMed  Google Scholar 

  10. Giorgi C, Marchi S, Simoes ICM, Ren Z, Morciano G, Perrone M et al (2018) Mitochondria and reactive oxygen species in aging and age-related diseases. Int Rev Cell Mol Biol 340:209–344. https://doi.org/10.1016/bs.ircmb.2018.05.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liesa M, Shirihai OS (2013) Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 17(4):491–506. https://doi.org/10.1016/j.cmet.2013.03.00210.1016/j.cmet.2013.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pernas L, Scorrano L (2016) Mito-morphosis: mitochondrial fusion, fission, and cristae remodeling as key mediators of cellular function. Annu Rev Physiol 78:505–31. https://doi.org/10.1146/annurev-physiol-021115-105011

    Article  CAS  PubMed  Google Scholar 

  13. Nunnari J, Suomalainen A (2012) Mitochondria: in sickness and in health. Cell 148(6):1145–1159. https://doi.org/10.1016/j.cell.2012.02.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Cartoni R, Arnaud E, Médard JJ, Poirot O, Courvoisier DS, Chrast R, Martinou JC (2010) Expression of mitofusin 2(R94Q) in a transgenic mouse leads to Charcot-Marie-Tooth neuropathy type 2A. Brain 133(Pt 5):1460–1469. https://doi.org/10.1093/brain/awq082

    Article  PubMed  Google Scholar 

  15. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S et al (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304(5674):1158–60. https://doi.org/10.1126/science.1096284

    Article  CAS  PubMed  Google Scholar 

  16. Chan DC (2006) Mitochondria: dynamic organelles in disease, aging, and development. Cell 125(7):1241–1252. https://doi.org/10.1016/j.cell.2006.06.010

    Article  CAS  PubMed  Google Scholar 

  17. Saito T, Sadoshima J (2015) Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circ Res 116(8):1477–1490. https://doi.org/10.1161/CIRCRESAHA.116.303790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yoon Y, Krueger EW, Oswald BJ, McNiven MA (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23(15):5409–5420. https://doi.org/10.1128/MCB.23.15.5409-5420.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Santel A, Fuller MT (2001) Control of mitochondrial morphology by a human mitofusin. J Cell Sci 114(Pt 5):867–874

    Article  CAS  PubMed  Google Scholar 

  20. Santel A, Frank S, Gaume B, Herrler M, Youle RJ, Fuller MT (2003) Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells. J Cell Sci 116(Pt 13):2763–2774. https://doi.org/10.1242/jcs.00479

    Article  CAS  PubMed  Google Scholar 

  21. Chen H, Detmer SA, Ewald AJ, Griffin EE, Fraser SE, Chan DC (2003) Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development. J Cell Biol 160(2):189–200. https://doi.org/10.1083/jcb.200211046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Griparic L, van der Wel NN, Orozco IJ, Peters PJ, van der Bliek AM (2004) Loss of the intermembrane space protein Mgm1/OPA1 induces swelling and localized constrictions along the lengths of mitochondria. J Biol Chem 279(18):18792–18798. https://doi.org/10.1074/jbc.M400920200

    Article  CAS  PubMed  Google Scholar 

  23. Cipolat S, Martins de Brito O, Dal Zilio B, Scorrano L (2004) OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci U S A 101(45):15927–32. https://doi.org/10.1073/pnas.0407043101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tilokani L, Nagashima S, Paupe V, Prudent J (2018) Mitochondrial dynamics: overview of molecular mechanisms. Essays Biochem 62(3):341–360. https://doi.org/10.1042/EBC20170104

    Article  PubMed  PubMed Central  Google Scholar 

  25. Zhao YX, Cui M, Chen SF, Dong Q, Liu XY (2014) Amelioration of ischemic mitochondrial injury and Bax-dependent outer membrane permeabilization by Mdivi-1. CNS Neurosci Ther 20(6):528–538. https://doi.org/10.1111/cns.12266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tang YN, Zhang GF, Chen HL, Sun XP, Qin WW, Shi F et al (2020) Selective brain hypothermia-induced neuroprotection against focal cerebral ischemia/reperfusion injury is associated with Fis1 inhibition. Neural Regen Res 15(5):903–911. https://doi.org/10.4103/1673-5374.268973

    Article  PubMed  Google Scholar 

  27. Flippo KH, Lin Z, Dickey AS, Zhou X, Dhanesha NA, Walters GC et al (2020) Deletion of a neuronal Drp1 activator protects against cerebral ischemia. J Neurosci 40(15):3119–3129. https://doi.org/10.1523/JNEUROSCI.1926-19.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. He M, Ma Y, Wang R, Zhang J, Jing L, Li PA (2020) Deletion of mitochondrial uncoupling protein 2 exacerbates mitochondrial damage in mice subjected to cerebral ischemia and reperfusion injury under both normo- and hyperglycemic conditions. Int J Biol Sci 16(15):2788–2802. https://doi.org/10.7150/ijbs.48204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. He M, Zhang T, Fan Y, Ma Y, Zhang J, Jing L, Li PA (2020) Deletion of mitochondrial uncoupling protein 2 exacerbates mitophagy and cell apoptosis after cerebral ischemia and reperfusion injury in mice. Int J Med Sci 17(17):2869–2878. https://doi.org/10.7150/ijms.49849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kumar R, Bukowski MJ, Wider JM, Reynolds CA, Calo L, Lepore B et al (2016) Mitochondrial dynamics following global cerebral ischemia. Mol Cell Neurosci 76:68–75. https://doi.org/10.1016/j.mcn.2016.08.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Klacanova K, Kovalska M, Chomova M, Pilchova I, Tatarkova Z, Kaplan P, Racay P (2019) Global brain ischemia in rats is associated with mitochondrial release and downregulation of Mfn2 in the cerebral cortex, but not the hippocampus. Int J Mol Med 43(6):2420–2428. https://doi.org/10.3892/ijmm.2019.4168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Lan S, Liu J, Luo X, Bi C (2019) Effects of melatonin on acute brain reperfusion stress: role of Hippo signaling pathway and MFN2-related mitochondrial protection. Cell Stress Chaperones 24(1):235–245. https://doi.org/10.1007/s12192-018-00960-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu Y, Shen J, Ran Z (2020) Emerging views of mitophagy in immunity and autoimmune diseases. Autophagy 16(1):3–17. https://doi.org/10.1080/15548627.2019.1603547

    Article  CAS  PubMed  Google Scholar 

  34. Wang Y, Cai J, Tang C, Dong Z (2020) Mitophagy in acute kidney injury and kidney repair. Cells 9(2):338. https://doi.org/10.3390/cells9020338

    Article  CAS  PubMed Central  Google Scholar 

  35. Xie Y, J Liu, R Kang, D Tang (2020) Mitophagy receptors in tumor biology. Front Cell Dev Biol 8(594203). https://doi.org/10.3389/fcell.2020.594203

  36. Fivenson EM, Lautrup S, Sun N, Scheibye-Knudsen M, Stevnsner T, Nilsen H et al (2017) Mitophagy in neurodegeneration and aging. Neurochem Int 109:202–209. https://doi.org/10.1016/j.neuint.2017.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sidarala V, GL Pearson, VS Parekh, B Thompson, L Christen, MA Gingerich, et al (2020) Mitophagy protects β cells from inflammatory damage in diabetes. JCI Insight 5(24). https://doi.org/10.1172/jci.insight.141138

  38. Fang EF, Hou Y, Palikaras K, Adriaanse BA, Kerr JS, Yang B et al (2019) Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat Neurosci 22(3):401–412. https://doi.org/10.1038/s41593-018-0332-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Liu Q, Zhang D, Hu D, Zhou X, Zhou Y (2018) The role of mitochondria in NLRP3 inflammasome activation. Mol Immunol 103:115–124. https://doi.org/10.1016/j.molimm.2018.09.010

    Article  CAS  PubMed  Google Scholar 

  40. Ott M, Robertson JD, Gogvadze V, Zhivotovsky B, Orrenius S (2002) Cytochrome c release from mitochondria proceeds by a two-step process. Proc Natl Acad Sci U S A 99(3):1259–1263. https://doi.org/10.1073/pnas.241655498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Galluzzi L, Kepp O, Kroemer G (2012) Mitochondria: master regulators of danger signalling. Nat Rev Mol Cell Biol 13(12):780–788. https://doi.org/10.1038/nrm3479

    Article  CAS  PubMed  Google Scholar 

  42. Hertz L (2008) Bioenergetics of cerebral ischemia: a cellular perspective. Neuropharmacology 55(3):289–309. https://doi.org/10.1016/j.neuropharm.2008.05.023

    Article  CAS  PubMed  Google Scholar 

  43. Puri R, Cheng X, Lin M, Huang N, Sheng Z (2019) Mul1 restrains Parkin-mediated mitophagy in mature neurons by maintaining ER-mitochondrial contacts. Nat Commun 10(1):3645. https://doi.org/10.1038/s41467-019-11636-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Puri R, Cheng X, Lin M, Huang N, Sheng Z (2020) Defending stressed mitochondria: uncovering the role of MUL1 in suppressing neuronal mitophagy. Autophagy 16(1):176–178. https://doi.org/10.1080/15548627.2019.1687216

    Article  CAS  PubMed  Google Scholar 

  45. Webster KA (2012) Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future Cardiol 8(6):863–884. https://doi.org/10.2217/fca.12.58

    Article  CAS  PubMed  Google Scholar 

  46. Meeusen SL, Nunnari J (2005) How mitochondria fuse. Curr Opin Cell Biol 17(4):389–394. https://doi.org/10.1016/j.ceb.2005.06.014

    Article  CAS  PubMed  Google Scholar 

  47. Gomes LC, Scorrano L (2008) High levels of Fis1, a pro-fission mitochondrial protein, trigger autophagy. Biochim Biophys Acta 1777(7–8):860–866. https://doi.org/10.1016/j.bbabio.2008.05.442

    Article  CAS  PubMed  Google Scholar 

  48. Xu B, Zhu L, Chu J, Ma Z, Fu Q, Wei W et al (2019) Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy. Behav Brain Res 372:112007. https://doi.org/10.1016/j.bbr.2019.112007

    Article  CAS  PubMed  Google Scholar 

  49. Wu W, Li W, Chen H, Jiang L, Zhu R, Feng D (2016) FUNDC1 is a novel mitochondrial-associated-membrane (MAM) protein required for hypoxia-induced mitochondrial fission and mitophagy. Autophagy 12(9):1675–1676. https://doi.org/10.1080/15548627.2016.1193656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Li S, Lin Q, Shao X, Zhu X, Wu J, Wu B et al (2020) Drp1-regulated PARK2-dependent mitophagy protects against renal fibrosis in unilateral ureteral obstruction. Free Radic Biol Med 152:632–649. https://doi.org/10.1016/j.freeradbiomed.2019.12.005

    Article  CAS  PubMed  Google Scholar 

  51. Wu Q, Gao C, Wang H, Zhang X, Li Q, Gu Z et al (2018) Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation. Int J Biochem Cell Biol 94:44–55. https://doi.org/10.1016/j.biocel.2017.11.007

    Article  CAS  PubMed  Google Scholar 

  52. Ma M, Lin XH, Liu HH, Zhang R, Chen RX (2020) Suppression of DRP1-mediated mitophagy increases the apoptosis of hepatocellular carcinoma cells in the setting of chemotherapy. Oncol Rep 43(3):1010–1018. https://doi.org/10.3892/or.2020.7476

    Article  CAS  PubMed  Google Scholar 

  53. Ni XX, Nie J, Xie QY, Yu RH, Su L, Liu ZF (2020) Protective effects of hyperbaric oxygen therapy on brain injury by regulating the phosphorylation of Drp1 through ROS/PKC pathway in heatstroke rats. Cell Mol Neurobiol 40(8):1253–1269. https://doi.org/10.1007/s10571-020-00811-8

    Article  CAS  PubMed  Google Scholar 

  54. Zuo W, Zhang S, Xia CY, Guo XF, He WB, Chen NH (2014) Mitochondria autophagy is induced after hypoxic/ischemic stress in a Drp1 dependent manner: the role of inhibition of Drp1 in ischemic brain damage. Neuropharmacology 86:103–115. https://doi.org/10.1016/j.neuropharm.2014.07.002

    Article  CAS  PubMed  Google Scholar 

  55. Denton K, Mou Y, Xu CC, Shah D, Chang J, Blackstone C, Li XJ (2018) Impaired mitochondrial dynamics underlie axonal defects in hereditary spastic paraplegias. Hum Mol Genet 27(14):2517–2530. https://doi.org/10.1093/hmg/ddy156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gao J, Luo A, Yan J, Fang X, Tang X, Zhao Y, Li S (2018) Mdivi-1 pretreatment mitigates isoflurane-induced cognitive deficits in developmental rats. Am J Transl Res 10(2):432–443

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Murata D, Arai K, Iijima M, Sesaki H (2020) Mitochondrial division, fusion and degradation. J Biochem 167(3):233–241. https://doi.org/10.1093/jb/mvz106

    Article  CAS  PubMed  Google Scholar 

  58. Morales PE, Arias-Durán C, Ávalos-Guajardo Y, Aedo G, Verdejo HE, Parra V, Lavandero S (2020) Emerging role of mitophagy in cardiovascular physiology and pathology. Mol Aspects Med 71:100822. https://doi.org/10.1016/j.mam.2019.09.006

    Article  PubMed  Google Scholar 

  59. Dorn GW 2nd, Kitsis RN (2015) The mitochondrial dynamism-mitophagy-cell death interactome: multiple roles performed by members of a mitochondrial molecular ensemble. Circ Res 116(1):167–182. https://doi.org/10.1161/CIRCRESAHA.116.303554

    Article  CAS  PubMed  Google Scholar 

  60. Eiyama A, Okamoto K (2015) PINK1/Parkin-mediated mitophagy in mammalian cells. Curr Opin Cell Biol 33:95–101. https://doi.org/10.1016/j.ceb.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  61. Quinn PMJ, Moreira PI, Ambrósio AF, Alves CH (2020) PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. Acta Neuropathol Commun 8(1):189. https://doi.org/10.1186/s40478-020-01062-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Deas E, Plun-Favreau H, Gandhi S, Desmond H, Kjaer S, Loh SH et al (2011) PINK1 cleavage at position A103 by the mitochondrial protease PARL. Hum Mol Genet 20(5):867–879. https://doi.org/10.1093/hmg/ddq526

    Article  CAS  PubMed  Google Scholar 

  63. Poole AC, Thomas RE, Andrews LA, McBride HM, Whitworth AJ, Pallanck LJ (2008) The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A 105(5):1638–1643. https://doi.org/10.1073/pnas.0709336105

    Article  PubMed  PubMed Central  Google Scholar 

  64. Tanaka K (2020) The PINK1-Parkin axis: an overview. Neurosci Res 159:9–15. https://doi.org/10.1016/j.neures.2020.01.006

    Article  CAS  PubMed  Google Scholar 

  65. Whitworth AJ, Pallanck LJ (2009) The PINK1/Parkin pathway: a mitochondrial quality control system? J Bioenerg Biomembr 41(6):499–503. https://doi.org/10.1007/s10863-009-9253-3

    Article  CAS  PubMed  Google Scholar 

  66. Rasool S, N Soya, L Truong, N Croteau, GL Lukacs, JF Trempe (2018) PINK1 autophosphorylation is required for ubiquitin recognition. EMBO Rep 19(4). https://doi.org/10.15252/embr.201744981

  67. Guardia-Laguarta C, Liu Y, Lauritzen KH, Erdjument-Bromage H, Martin B, Swayne TC et al (2019) PINK1 Content in mitochondria is regulated by ER-associated degradation. J Neurosci 39(36):7074–7085. https://doi.org/10.1523/JNEUROSCI.1691-18.2019

    Article  PubMed  PubMed Central  Google Scholar 

  68. Okatsu K, Koyano F, Kimura M, Kosako H, Saeki Y, Tanaka K, Matsuda N (2015) Phosphorylated ubiquitin chain is the genuine Parkin receptor. J Cell Biol 209(1):111–128. https://doi.org/10.1083/jcb.201410050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Yamano K, Matsuda N, Tanaka K (2016) The ubiquitin signal and autophagy: an orchestrated dance leading to mitochondrial degradation. EMBO Rep 17(3):300–16. https://doi.org/10.15252/embr.201541486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Iguchi M, Kujuro Y, Okatsu K, Koyano F, Kosako H, Kimura M et al (2013) Parkin-catalyzed ubiquitin-ester transfer is triggered by PINK1-dependent phosphorylation. J Biol Chem 288(30):22019–22032. https://doi.org/10.1074/jbc.M113.467530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kondapalli C, Kazlauskaite A, Zhang N, Woodroof HI, Campbell DG, Gourlay R et al (2012) PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol 2(5):120080. https://doi.org/10.1098/rsob.120080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kazlauskaite A, Kondapalli C, Gourlay R, Campbell DG, Ritorto MS, Hofmann K et al (2014) Parkin is activated by PINK1-dependent phosphorylation of ubiquitin at Ser65. Biochem J 460(1):127–139. https://doi.org/10.1042/BJ20140334

    Article  CAS  PubMed  Google Scholar 

  73. Chen Y, Dorn GW 2nd (2013) PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria. Science 340(6131):471–475. https://doi.org/10.1126/science.1231031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803. https://doi.org/10.1083/jcb.200809125

    Article  PubMed  PubMed Central  Google Scholar 

  75. Wauer T, Simicek M, Schubert A, Komander D (2015) Mechanism of phospho-ubiquitin-induced PARKIN activation. Nature 524(7565):370–374. https://doi.org/10.1038/nature14879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Georgakopoulos ND, Wells G, Campanella M (2017) The pharmacological regulation of cellular mitophagy. Nat Chem Biol 13(2):136–146. https://doi.org/10.1038/nchembio.2287

    Article  CAS  PubMed  Google Scholar 

  77. Ashrafi G, Schwarz TL (2013) The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 20(1):31–42. https://doi.org/10.1038/cdd.2012.81

    Article  CAS  PubMed  Google Scholar 

  78. Lazarou M, Sliter DA, Kane LA, Sarraf SA, Wang C, Burman JL et al (2015) The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524(7565):309–314. https://doi.org/10.1038/nature14893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Sandoval H, Thiagarajan P, Dasgupta SK, Schumacher A, Prchal JT, Chen M, Wang J (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454(7201):232–235. https://doi.org/10.1038/nature07006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Kubli DA, Ycaza JE, Gustafsson AB (2007) Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak. Biochem J 405(3):407–415. https://doi.org/10.1042/BJ20070319

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Zhang J, Ney PA (2009) Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16(7):939–946. https://doi.org/10.1038/cdd.2009.16

    Article  CAS  PubMed  Google Scholar 

  82. Rogov VV, Suzuki H, Marinković M, Lang V, Kato R, Kawasaki M et al (2017) Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins. Sci Rep 7(1):1131. https://doi.org/10.1038/s41598-017-01258-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouysségur J, Mazure NM (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29(10):2570–2581. https://doi.org/10.1128/MCB.00166-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P et al (2007) FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab 6(6):458–471. https://doi.org/10.1016/j.cmet.2007.11.001

    Article  CAS  PubMed  Google Scholar 

  85. Sowter HM, Ratcliffe PJ, Watson P, Greenberg AH, Harris AL (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Cancer Res 61(18):6669–6673

    CAS  PubMed  Google Scholar 

  86. Liu XW, Lu MK, Zhong HT, Wang LH, Fu YP (2019) Panax notoginseng saponins attenuate myocardial ischemia-reperfusion injury through the HIF-1α/BNIP3 pathway of autophagy. J Cardiovasc Pharmacol 73(2):92–99. https://doi.org/10.1097/FJC.0000000000000640

    Article  CAS  PubMed  Google Scholar 

  87. Novak I, Kirkin V, McEwan DG, Zhang J, Wild P, Rozenknop A et al (2010) Nix is a selective autophagy receptor for mitochondrial clearance. EMBO Rep 11(1):45–51. https://doi.org/10.1038/embor.2009.256

    Article  CAS  PubMed  Google Scholar 

  88. Shi RY, Zhu SH, Li V, Gibson SB, Xu XS, Kong JM (2014) BNIP3 interacting with LC3 triggers excessive mitophagy in delayed neuronal death in stroke. CNS Neurosci Ther 20(12):1045–1055. https://doi.org/10.1111/cns.12325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Jung J, Zhang Y, Celiku O, Zhang W, Song H, Williams BJ et al (2019) Mitochondrial NIX promotes tumor survival in the hypoxic niche of glioblastoma. Cancer Res 79(20):5218–5232. https://doi.org/10.1158/0008-5472.CAN-19-0198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Ding WX, Ni HM, Li M, Liao Y, Chen X, Stolz DB et al (2010) Nix is critical to two distinct phases of mitophagy, reactive oxygen species-mediated autophagy induction and Parkin-ubiquitin-p62-mediated mitochondrial priming. J Biol Chem 285(36):27879–27890. https://doi.org/10.1074/jbc.M110.119537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Liu L, Feng D, Chen G, Chen M, Zheng Q, Song P et al (2012) Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol 14(2):177–185. https://doi.org/10.1038/ncb2422

    Article  CAS  PubMed  Google Scholar 

  92. Zhang W, Siraj S, Zhang R, Chen Q (2017) Mitophagy receptor FUNDC1 regulates mitochondrial homeostasis and protects the heart from I/R injury. Autophagy 13(6):1080–1081. https://doi.org/10.1080/15548627.2017.1300224

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Cai Y, Yang E, Yao X, Zhang X, Wang Q, Wang Y et al (2021) FUNDC1-dependent mitophagy induced by tPA protects neurons against cerebral ischemia-reperfusion injury. Redox Biol 38:101792. https://doi.org/10.1016/j.redox.2020.101792

    Article  CAS  PubMed  Google Scholar 

  94. Chen M, Chen Z, Wang Y, Tan Z, Zhu C, Li Y et al (2016) Mitophagy receptor FUNDC1 regulates mitochondrial dynamics and mitophagy. Autophagy 12(4):689–702. https://doi.org/10.1080/15548627.2016.1151580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Kuang Y, Ma K, Zhou C, Ding P, Zhu Y, Chen Q, Xia B (2016) Structural basis for the phosphorylation of FUNDC1 LIR as a molecular switch of mitophagy. Autophagy 12(12):2363–2373. https://doi.org/10.1080/15548627.2016.1238552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Chen G, Han Z, Feng D, Chen Y, Chen L, Wu H et al (2014) A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell 54(3):362–377. https://doi.org/10.1016/j.molcel.2014.02.034

    Article  CAS  PubMed  Google Scholar 

  97. Lo EH, Dalkara T, Moskowitz MA (2003) Mechanisms, challenges and opportunities in stroke. Nat Rev Neurosci 4(5):399–415. https://doi.org/10.1038/nrn1106

    Article  CAS  PubMed  Google Scholar 

  98. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL et al (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515(7527):431–435. https://doi.org/10.1038/nature13909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Li H, Xia Z, Chen Y, Qi D, Zheng H (2018) Mechanism and therapies of oxidative stress-mediated cell death in ischemia reperfusion injury. Oxid Med Cell Longev 2018:2910643. https://doi.org/10.1155/2018/2910643

    Article  PubMed  PubMed Central  Google Scholar 

  100. Panel M, Ruiz I, Brillet R, Lafdil F, Teixeira-Clerc F, Nguyen CT et al (2019) Small-molecule inhibitors of cyclophilins block opening of the mitochondrial permeability transition pore and protect mice from hepatic ischemia/reperfusion injury. Gastroenterology 157(5):1368–1382. https://doi.org/10.1053/j.gastro.2019.07.026

    Article  CAS  PubMed  Google Scholar 

  101. Wang Y, Nartiss Y, Steipe B, McQuibban GA, Kim PK (2012) ROS-induced mitochondrial depolarization initiates PARK2/PARKIN-dependent mitochondrial degradation by autophagy. Autophagy 8(10):1462–1476. https://doi.org/10.4161/auto.21211

    Article  CAS  PubMed  Google Scholar 

  102. Bonora M, Giorgi C, Pinton P (2021) Molecular mechanisms and consequences of mitochondrial permeability transition. Nat Rev Mol Cell Biol. https://doi.org/10.1089/ars.2021.0275

    Article  PubMed  Google Scholar 

  103. Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW et al (2018) Current Mechanistic Concepts in ischemia and reperfusion injury. Cell Physiol Biochem 46(4):1650–1667. https://doi.org/10.1159/000489241

    Article  CAS  PubMed  Google Scholar 

  104. Kim H, Scimia MC, Wilkinson D, Trelles RD, Wood MR, Bowtell D et al (2011) Fine-tuning of Drp1/Fis1 availability by AKAP121/Siah2 regulates mitochondrial adaptation to hypoxia. Mol Cell 44(4):532–544. https://doi.org/10.1016/j.molcel.2011.08.045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kim J, Kundu M, Viollet B, Guan KL (2011) AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 13(2):132–141. https://doi.org/10.1038/ncb2152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Zaha VG, Young LH (2012) AMP-activated protein kinase regulation and biological actions in the heart. Circ Res 111(6):800–814. https://doi.org/10.1161/CIRCRESAHA.111.255505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Kundu M, Lindsten T, Yang CY, Wu J, Zhao F, Zhang J et al (2008) Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticulocyte maturation. Blood 112(4):1493–1502. https://doi.org/10.1182/blood-2008-02-137398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Zhou Y, Zhang S, Fan X (2021) Role of polyphenols as antioxidant supplementation in ischemic stroke. Oxid Med Cell Longev 2021:5471347. https://doi.org/10.1155/2021/5471347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Jakic B, Carlsson M, Buszko M, Cappellano G, Ploner C, Onestingel E et al (2018) The effects of endurance exercise and diet on atherosclerosis in young and aged ApoE–/– and wild-type mice. Gerontology 30:1–12. https://doi.org/10.1159/000492571

    Article  CAS  Google Scholar 

  110. Scherz-Shouval R, E Shvets, E Fass, H Shorer, L Gil, Z Elazar (2019) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. Embo J 38(10). https://doi.org/10.15252/embj.2019101812

  111. Alexander A, Cai SL, Kim J, Nanez A, Sahin M, MacLean KH et al (2010) ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc Natl Acad Sci U S A 107(9):4153–4158. https://doi.org/10.1073/pnas.0913860107

    Article  PubMed  PubMed Central  Google Scholar 

  112. Lan R, Wu JT, Wu T, Ma YZ, Wang BQ, Zheng HZ et al (2018) Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1/Parkin/p62 signalling pathway. Brain Res Bull 142:63–77. https://doi.org/10.1016/j.brainresbull.2018.06.018

    Article  CAS  PubMed  Google Scholar 

  113. Wang W, Xu J (2020) Curcumin attenuates cerebral ischemia-reperfusion injury through regulating mitophagy and preserving mitochondrial function. Curr Neurovasc Res 17(2):113–122. https://doi.org/10.2174/1567202617666200225122620

    Article  CAS  PubMed  Google Scholar 

  114. Li F, Tan J, Zhou F, Hu Z, Yang B (2018) Heat shock protein B8 (HSPB8) reduces oxygen-glucose deprivation/reperfusion injury via the induction of mitophagy. Cell Physiol Biochem 48(4):1492–1504. https://doi.org/10.1159/000492259

    Article  CAS  PubMed  Google Scholar 

  115. Wang H, Chen S, Zhang Y, Xu H, Sun H (2019) Electroacupuncture ameliorates neuronal injury by Pink1/Parkin-mediated mitophagy clearance in cerebral ischemia-reperfusion. Nitric Oxide 91:23–34. https://doi.org/10.1016/j.niox.2019.07.004

    Article  CAS  PubMed  Google Scholar 

  116. Wu M, Lu G, Lao YZ, Zhang H, Zheng D, Zheng ZQ et al (2021) Garciesculenxanthone B induces PINK1-Parkin-mediated mitophagy and prevents ischemia-reperfusion brain injury in mice. Acta Pharmacol Sin 42(2):199–208. https://doi.org/10.1038/s41401-020-0480-9

    Article  CAS  PubMed  Google Scholar 

  117. Baek SH, Noh AR, Kim KA, Akram M, Shin YJ, Kim ES et al (2014) Modulation of mitochondrial function and autophagy mediates carnosine neuroprotection against ischemic brain damage. Stroke 45(8):2438–2443. https://doi.org/10.1161/STROKEAHA.114.005183

    Article  PubMed  PubMed Central  Google Scholar 

  118. Shen Z, Zheng Y, Wu J, Chen Y, Wu X, Zhou Y et al (2017) PARK2-dependent mitophagy induced by acidic postconditioning protects against focal cerebral ischemia and extends the reperfusion window. Autophagy 13(3):473–485. https://doi.org/10.1080/15548627.2016.1274596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Li Q, Zhang T, Wang J, Zhang Z, Zhai Y, Yang GY, Sun X (2014) Rapamycin attenuates mitochondrial dysfunction via activation of mitophagy in experimental ischemic stroke. Biochem Biophys Res Commun 444(2):182–188. https://doi.org/10.1016/j.bbrc.2014.01.032

    Article  CAS  PubMed  Google Scholar 

  120. Yuan Y, Zheng Y, Zhang X, Chen Y, Wu X, Wu J et al (2017) BNIP3L/NIX-mediated mitophagy protects against ischemic brain injury independent of PARK2. Autophagy 13(10):1754–1766. https://doi.org/10.1080/15548627.2017.1357792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Wu X, Li X, Liu Y, Yuan N, Li C, Kang Z et al (2018) Hydrogen exerts neuroprotective effects on OGD/R damaged neurons in rat hippocampal by protecting mitochondrial function via regulating mitophagy mediated by PINK1/Parkin signaling pathway. Brain Res 1698:89–98. https://doi.org/10.1016/j.brainres.2018.06.028

    Article  CAS  PubMed  Google Scholar 

  122. He Q, Li Z, Meng C, Wu J, Zhao Y, Zhao J (2019) Parkin-dependent mitophagy is required for the inhibition of ATF4 on NLRP3 inflammasome activation in cerebral ischemia-reperfusion injury in rats. Cells 8(8):897. https://doi.org/10.3390/cells8080897

    Article  CAS  PubMed Central  Google Scholar 

  123. Kulek AR, Anzell A, Wider JM, Sanderson TH, Przyklenk K (2020) Mitochondrial quality control: role in cardiac models of lethal ischemia-reperfusion injury. Cells 9(1):214. https://doi.org/10.3390/cells9010214

    Article  CAS  PubMed Central  Google Scholar 

  124. Wang R, Dong Y, Lu Y, Zhang W, Brann DW, Zhang Q (2019) Photobiomodulation for global cerebral ischemia: targeting mitochondrial dynamics and functions. Mol Neurobiol 56(3):1852–1869. https://doi.org/10.1007/s12035-018-1191-9

    Article  CAS  PubMed  Google Scholar 

  125. Zhang X, Yan H, Yuan Y, Gao J, Shen Z, Cheng Y et al (2013) Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance. Autophagy 9(9):1321–1333. https://doi.org/10.4161/auto.25132

    Article  CAS  PubMed  Google Scholar 

  126. Deng Z, Ou H, Ren F, Guan Y, Huan Y, Cai H et al (2020) LncRNA SNHG14 promotes OGD/R-induced neuron injury by inducing excessive mitophagy via miR-182-5p/BINP3 axis in HT22 mouse hippocampal neuronal cells. Biol Res 53(1):38. https://doi.org/10.1186/s40659-020-00304-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Zhang Y, He Y, Wu M, Chen H, Zhang L, Yang D et al (2020) Rehmapicroside ameliorates cerebral ischemia-reperfusion injury via attenuating peroxynitrite-mediated mitophagy activation. Free Radic Biol Med 160:526–539. https://doi.org/10.1016/j.freeradbiomed.2020.06.034

    Article  CAS  PubMed  Google Scholar 

  128. Lan R, Zhang Y, Wu T, Ma YZ, Wang BQ, Zheng HZ et al (2018) Xiao-Xu-Ming Decoction reduced mitophagy activation and improved mitochondrial function in cerebral ischemia and reperfusion injury. Behav Neurol 2018:4147502. https://doi.org/10.1155/2018/4147502

    Article  PubMed  PubMed Central  Google Scholar 

  129. Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M (2013) Impaired autophagy and APP processing in Alzheimer’s disease: the potential role of beclin 1 interactome. Prog Neurobiol 106–107:33–54. https://doi.org/10.1016/j.pneurobio.2013.06.002

    Article  CAS  PubMed  Google Scholar 

  130. Papadakis M, Hadley G, Xilouri M, Hoyte LC, Nagel S, McMenamin MM et al (2013) Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy. Nat Med 19(3):351–357. https://doi.org/10.1038/nm.3097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y (1998) Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 23(1):33–42. https://doi.org/10.1247/csf.23.33

    Article  CAS  PubMed  Google Scholar 

  132. Mauthe M, Orhon I, Rocchi C, Zhou X, Luhr M, Hijlkema KJ et al (2018) Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion. Autophagy 14(8):1435–1455. https://doi.org/10.1080/15548627.2018.1474314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Hou H, Zhang Y, Huang Y, Yi Q, Lv L, Zhang T et al (2012) Inhibitors of phosphatidylinositol 3’-kinases promote mitotic cell death in HeLa cells. PLoS ONE 7(4):e35665. https://doi.org/10.1371/journal.pone.0035665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Zhou Y, Men L, Sun Y, Wei M, Fan X (2021) Pharmacodynamic effects and molecular mechanisms of lignans from Schisandra chinensis Turcz. (Baill.), a current review. Eur J Pharmacol 892:173796. https://doi.org/10.1016/j.ejphar.2020.173796

    Article  CAS  PubMed  Google Scholar 

  135. Pineda-Ramírez N, Alquisiras-Burgos I, Ortiz-Plata A, Ruiz-Tachiquín ME, Espinoza-Rojo M, Aguilera P (2020) Resveratrol activates neuronal autophagy through AMPK in the ischemic brain. Mol Neurobiol 57(2):1055–1069. https://doi.org/10.1007/s12035-019-01803-6

    Article  CAS  PubMed  Google Scholar 

  136. He Q, Li Z, Wang Y, Hou Y, Li L, Zhao J (2017) Resveratrol alleviates cerebral ischemia/reperfusion injury in rats by inhibiting NLRP3 inflammasome activation through Sirt1-dependent autophagy induction. Int Immunopharmacol 50:208–215. https://doi.org/10.1016/j.intimp.2017.06.029

    Article  CAS  PubMed  Google Scholar 

  137. Fan W, Chen S, Wu X, Zhu J, Li J (2021) Resveratrol relieves gouty arthritis by promoting mitophagy to inhibit activation of NLRP3 inflammasomes. J Inflamm Res 14:3523–3536. https://doi.org/10.2147/JIR.S320912

    Article  PubMed  PubMed Central  Google Scholar 

  138. Zenkov NK, Chechushkov AV, Kozhin PM, Kandalintseva NV, Martinovich GG, Menshchikova EB (2016) Plant phenols and autophagy. Biochemistry (Mosc) 81(4):297–314. https://doi.org/10.1134/S0006297916040015

    Article  CAS  Google Scholar 

  139. Cui WH, Zhang HH, Qu ZM, Wang Z, Zhang DJ, Wang S (2020) Effects of chrysophanol on hippocampal damage and mitochondrial autophagy in mice with cerebral ischemia reperfusion. Int J Neurosci 1–8. https://doi.org/10.1080/00207454.2020.1830085

  140. Pan J, X Li, F Guo, Z Yang, L Zhang, C Yang (2019) Ginkgetin attenuates cerebral ischemia-reperfusion induced autophagy and cell death via modulation of the NF-κB/p53 signaling pathway. Biosci Rep 39(9). https://doi.org/10.1042/BSR20191452

  141. Vijayakumaran S, Nakamura Y, Henley JM, Pountney DL (2019) Ginkgolic acid promotes autophagy-dependent clearance of intracellular alpha-synuclein aggregates. Mol Cell Neurosci 101:103416. https://doi.org/10.1016/j.mcn.2019.103416

    Article  CAS  PubMed  Google Scholar 

  142. Liu S, Su Y, Sun B, Hao R, Pan S, Gao X et al (2020) Luteolin protects against CIRI, potentially via regulation of the SIRT3/AMPK/mTOR signaling pathway. Neurochem Res 45(10):2499–2515. https://doi.org/10.1007/s11064-020-03108-w

    Article  CAS  PubMed  Google Scholar 

  143. Kunz A, Dirnagl U, Mergenthaler P (2010) Acute pathophysiological processes after ischaemic and traumatic brain injury. Best Pract Res Clin Anaesthesiol 24(4):495–509. https://doi.org/10.1016/j.bpa.2010.10.001

    Article  CAS  PubMed  Google Scholar 

  144. Jendrach M, Mai S, Pohl S, Vöth M, Bereiter-Hahn J (2008) Short- and long-term alterations of mitochondrial morphology, dynamics and mtDNA after transient oxidative stress. Mitochondrion 8(4):293–304. https://doi.org/10.1016/j.mito.2008.06.001

    Article  CAS  PubMed  Google Scholar 

  145. Singh A, Mahajan SD, Kutscher HL, Kim S, Prasad PN (2020) Curcumin-pluronic nanoparticles: a theranostic nanoformulation for Alzheimer’s disease. Crit Rev Biomed Eng 48(3):153–168. https://doi.org/10.1615/CritRevBiomedEng.2020034302

    Article  PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (NO.82174047, 81622051), Zhejiang Provincial Natural Science Foundation of China (NO.LY22H280004) and Foundation of Zhejiang Chinese Medical University (No.2020ZR20).

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All authors contributed to the study conception and design. MS and XF conceived and designed the review. MS did the literature searches, did data interpretation, and manuscript writing. YZ did manuscript writing and developed the figure. XF reviewed and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Xiang Fan.

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Song, M., Zhou, Y. & Fan, X. Mitochondrial Quality and Quantity Control: Mitophagy Is a Potential Therapeutic Target for Ischemic Stroke. Mol Neurobiol 59, 3110–3123 (2022). https://doi.org/10.1007/s12035-022-02795-6

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