Abstract
Lysosomes are single membrane-bound organelles containing acid hydrolases responsible for the degradation of cellular cargo and maintenance of cellular homeostasis. Lysosomes could originate from pre-existing endolysosomes or autolysosomes, acting as a critical juncture between autophagy and endocytosis. Stress that triggers lysosomal membrane permeabilization can be altered by ESCRT complexes; however, irreparable damage to the membrane results in the induction of a selective lysosomal degradation pathway, specifically lysophagy. Lysosomes play an indispensable role in different types of autophagy, including microautophagy, macroautophagy, and chaperone-mediated autophagy, and various cell death pathways such as lysosomal cell death, apoptotic cell death, and autophagic cell death. In this review, we discuss lysosomal reformation, maintenance, and degradation pathways following the involvement of the lysosome in autophagy and cell death, which are related to several pathophysiological conditions observed in humans.
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Abbreviations
- TFEB:
-
Transcription factor EB
- mTORC1:
-
Mechanistic target of rapamycin complex 1
- VAMP7:
-
Vesicle associated membrane Protein 7
- VAMP8:
-
Vesicle associated membrane Protein 8
- NSF:
-
N-Ethylmaleimide sensitive factor
- SNAP:
-
Soluble NSF attachment proteins
- RILP:
-
Rab-interacting lysosomal protein
- p70S6K1:
-
P70-S6 kinase 1
- LAMP1:
-
Lysosomal-associated membrane protein 1
- ATF4:
-
Activating transcription factor 4
- WASP:
-
Wiskott-Aldrich syndrome protein
- PIP5K1B:
-
PtdIns(4)P-5-kinase-1-baeta
- KIF5B:
-
Kinesin family member 5B
- UVRAG:
-
UV radiation resistance-associated gene
- DNM2:
-
Dynamin2
- CHMP4B:
-
Charged multivesicular body protein 4B
- TRIM16:
-
Tripartite motif containing 16
- UBE2QL1:
-
Ubiquitin conjugating enzyme E2 Q family like 1
- ULK1:
-
Unc-51 like autophagy activating kinase-1
- FIP200:
-
Focal adhesion kinase family interacting protein of 200 kDa
- BECN1:
-
Beclin1
- WIPI1:
-
WD repeat domain, phosphoinositide interacting 1
- NRBF2:
-
Nuclear receptor-binding factor 2
- STX-17:
-
Syntaxin-17
- TECPR1:
-
Tectonin beta-propeller repeat containing 1
- Hsc70:
-
Heat shock cognate 71 kDa protein
- Hsp40:
-
Heat shock protein of 40 kDa
- hip:
-
Hsc70 interacting protein
- hop:
-
Hsc70-hsp90 organizer protein
- Hsp90:
-
Heat shock protein of 90 kDa
- bag-1:
-
Bcl2-associated athanogene-1
- caspase:
-
Cysteine-dependent aspartate-directed proteases
- LIMP2:
-
Lysosomal integral membrane protein type-2
- Apaf1:
-
Apoptotic protease-activating factor 1
- DRAM1:
-
DNA damage-regulated autophagy modulator
- DAPK1:
-
Death-associated protein kinase 1
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Acknowledgements
KKM is highly acknowledged by the Government of India, Ministry of Science & Technology, Department of Science and Technology (No. DST/INSPIRE Fellowship/2017/IF170344). Research support was partly provided by the Science and Engineering Research Board (SERB) [EMR/2016/001246], Department of Science and Technology.
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Mahapatra, K.K., Mishra, S.R., Behera, B.P. et al. The lysosome as an imperative regulator of autophagy and cell death. Cell. Mol. Life Sci. 78, 7435–7449 (2021). https://doi.org/10.1007/s00018-021-03988-3
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DOI: https://doi.org/10.1007/s00018-021-03988-3