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3,5-Diiodo-L-Thyronine increases FoF1-ATP synthase activity and cardiolipin level in liver mitochondria of hypothyroid rats

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Abstract

Short-term effects of 3,5-L-diiodothyronine (T2) administration to hypothyroid rats on FoF1-ATP synthase activity were investigated in liver mitochondria. One hour after T2 injection, state 4 and state 3 respiration rates were noticeably stimulated in mitochondria subsequently isolated. FoF1-ATP synthase activity, which was reduced in mitochondria from hypothyroid rats as compared to mitochondria from euthyroid rats, was significantly increased by T2 administration in both the ATP-synthesis and hydrolysis direction. No change in β-subunit mRNA accumulation and protein amount of the α-β subunit of FoF1-ATP synthase was found, ruling out a T2 genomic effect. In T2-treated rats, changes in the composition of mitochondrial phospholipids were observed, cardiolipin (CL) showing the greatest alteration. In mitochondria isolated from hypothyroid rats the decrease in the amount of CL was accompanied by an increase in the level of peroxidised CL. T2 administration to hypothyroid rats enhanced the level of CL and decreased the amount of peroxidised CL in subsequently isolated mitochondria, tending to restore the CL value to the euthyroid level. Minor T2-induced changes in mitochondrial fatty acid composition were detected. Overall, the enhanced FoF1-ATP synthase activity observed following injection of T2 to hypothyroid rats may be ascribed, at least in part, to an increased level of mitochondrial CL associated with decreased peroxidation of CL.

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References

  • Arnold S, Goglia F, Kadenbach B (1998) 3,5-diiodothyronine binds to subunit Va of cytochrome-c oxidase and abolishes the allosteric inhibition of respiration by ATP. Eur J Biochem 252:325–330

    Article  CAS  Google Scholar 

  • Ball SG, Sokolov J, Chin WW (1997) 3,5-diiodo-l-thyronine T2 has selective thyromimetic effects in vivo and in vitro. J Mol Endocrinol 19:137–147

    Article  CAS  Google Scholar 

  • Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917

    Article  CAS  Google Scholar 

  • Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  CAS  Google Scholar 

  • Caputi Jambrenghi A, Paglialonga G, Gnoni A, Zanotti F, Giannico F, Vonghia G, Gnoni GV (2007) Changes in lipid composition and lipogenic enzyme activities in liver of lambs fed omega-6 polyunsaturated fatty acids. Comp Biochem Physiol Part B 147:498–503

    Article  CAS  Google Scholar 

  • Chicco AJ, Sparagna GC (2007) Role of cardiolipin alterations in mitochondrial dysfunction and disease. Am J Physiol Cell Physiol 292:C33–C44

    Article  CAS  Google Scholar 

  • Claypool SM, Oktay Y, Boontheung P, Loo JA, Koehler CM (2008) Cardiolipin defines the interactome of the major ADP/ATP carrier protein of the mitochondrial inner membrane. J Cell Biol 182:937–950

    Article  CAS  Google Scholar 

  • Das K, Chainy GB (2001) Modulation of rat liver mitochondrial antioxidant defence system by thyroid hormone. Biochim Biophys Acta 1537:1–13

    CAS  Google Scholar 

  • Dummler K, Muller S, Seitz HJ (1996) In rat liver, ant2 is the main isoform and its expression is regulated by T3. Biochem J 317:913–918

    Google Scholar 

  • Enrìquez JA, Fernàndez-Silva P, Garrido-Pérez N, López-Pérez MJ, Pérez-Martos A, Montoya J (1999) Direct regulation of mitochondrial RNA synthesis by thyroid hormone. Mol Cell Biol 19:657–670

    Google Scholar 

  • Eskola J, Laakso SS (1983) Bile salt-dependent oxygenation of polyunsatured phosphatidylcholines by soybean lipoxigenase-1. Biochim Biophys Acta 75:305–311

    Google Scholar 

  • Gay GA, Gebiki JM (2003) Measurement of protein and lipid hydroperoxides in biological systems by the ferric-xylenol orange method. Anal Biochem 315:29–35

    Article  CAS  Google Scholar 

  • Giudetti AM, Leo M, Geelen MJH, Gnoni GV (2005) Short-term stimulation of lipogenesis by 3,5-L-diiodothyronine in cultured rat hepatocytes. Endocrinology 146:3959–3966

    Article  CAS  Google Scholar 

  • Giudetti AM, Leo M, Siculella L, Gnoni GV (2006) Hypothyroidism down-regulates mitochondrial citrate carrier activity and expression in rat liver. Biochim Biophys Acta 176:484–491

    Google Scholar 

  • Goglia F (2005) Biological effects of 3,5-diiodothyronine (T2). Biochem Mosc 70:164–172

    Article  CAS  Google Scholar 

  • Goglia F, Moreno M, Lanni A (1999) Action of thyroid hormones at the cellular level: the mitochondrial target. FEBS Lett 452:115–120

    Article  CAS  Google Scholar 

  • Guerrieri F, Kalous M, Adorisio E, Turturro N, Santoro G, Drahota Z, Cantatore P (1998) Hypothyroidism leads to a decreased expression of mitochondrial FoF1-ATP synthase in rat liver. J Bioenerg Biomembr 30:269–276

    Article  CAS  Google Scholar 

  • Hafner RP, Brown GC, Brand MD (1990) Thyroid-hormone control of state-3 respiration in isolated rat liver mitochondria. Biochem J 265:731–734

    CAS  Google Scholar 

  • Hinkle PC (2005) P/O ratios of mitochondrial oxidative phosphorylation. Biochim Biophys Acta 1706:1–11

    Article  CAS  Google Scholar 

  • Hoffmann B, Stöckl A, Schlame M, Beyer K, Klingenberg M (1994) The reconstituted ADP/ATP carrier activity has an absolute requirement for cardiolipin as shown cysteine mutants. J Biol Chem 269:1940–1944

    CAS  Google Scholar 

  • Horst C, Rokos H, Seitz HJ (1989) Rapid stimulation of hepatic oxygen consumption by 3,5-di-iodo-L-thyronine. Biochem J 261:945–950

    CAS  Google Scholar 

  • Hulbert AJ (2000) Thyroid hormones and their effects: a new prospective. Biol Rev 75:519–631

    Article  CAS  Google Scholar 

  • Izquierdo JM, Cuezva JM (1993) Thyroid hormones promote transcriptional activation of the nuclear gene coding for mitochondrial beta-F1-ATPase in rat liver. FEBS Lett 323:109–112

    Article  CAS  Google Scholar 

  • Lombardi A, Lanni A, Moreno M, Brand MD, Goglia F (1998) Effect of 3,5-di-iodo-l-thyronine on the mitochondrial energy-transduction apparatus. Biochem J 330:521–526

    CAS  Google Scholar 

  • Lombardi A, Lanni A, De Lange P, Silvestri E, Grasso P, Senese R, Goglia F, Moreno M (2007) Acute administration of 3,5-diiodo-l-thyronine to hypothyroid rats affects bioenergetic parameters in rat skeletal muscle mitochondria. FEBS Lett 581:5911–5916

    Article  CAS  Google Scholar 

  • Lombardi A, De Lange P, Silvestri E, Busiello RA, Lanni A, Goglia F, Moreno M (2009) 3,5-Diiodo-L-thyronine rapidly enhances mitochondrial fatty acid oxidation rate and thermogenesis in rat skeletal muscle: AMP-activated protein kinase involvement. Am J Physiol Endocrinol Metabolism 296:E497–E502

    Article  CAS  Google Scholar 

  • Mangiullo R, Gnoni A, Damiano F, Siculella L, Zanotti F, Papa S, Gnoni GV (2010) 3,5-diiodo-l-thyronine upregulates rat-liver mitochondrial FoF1-ATP synthase by GA-binding protein/nuclear respiratory factor-2. Biochim Biophys Acta 1797:233–240

    Article  CAS  Google Scholar 

  • Moreno M, Lanni A, Lombardi A, Goglia F (1997) How the thyroid controls metabolism in the rat: different roles for triiodothyronine and diiodothyronines. J Physiol 505:529–538

    Article  CAS  Google Scholar 

  • Mrácek T, Jesina P, Krivácová P, Bolehovská R, Cervinková Z, Drahota Z, Houstek J (2005) Time-course of hormonal induction of mitochondrial glycerophosphate dehydrogenase biogenesis in rat liver. Biochim Biophys Acta 1726:217–223

    Google Scholar 

  • Nakamura GR (1952) Microdetermination of phosphorus. Anal Chem 24:1372

    Article  CAS  Google Scholar 

  • Nogueira V, Walter L, Avéret N, Fontaine E, Rigoulet M, Leverve XM (2002) Thyroid status is a key regulator of both flux and efficiency of oxidative phosphorylation in rat hepatocytes. J Bioenerg Biomembr 34:55–66

    Article  CAS  Google Scholar 

  • Paradies G, Ruggiero FM (1988) Effect of hyperthyroidism on the transport of pyruvate in rat-heart mitochondria. Biochim Biophys Acta 935:79–86

    Article  CAS  Google Scholar 

  • Paradies G, Ruggiero FM, Dinoi P (1991) The influence of hypothyroidism on the transport of phosphate and on the lipid composition in rat-liver mitochondria. Biochim Biophys Acta 1070:180–186

    Article  CAS  Google Scholar 

  • Paradies G, Petrosillo G, Paradies V, Ruggiero FM (2010) Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med 48:1286–1295

    Article  CAS  Google Scholar 

  • Petrosillo G, Portincasa P, Grattagliano I, Casanova G, Matera M, Ruggiero FM, Ferri D, Paradies G (2007) Mitochondrial dysfunction in rat with nonalcoholic fatty liver. Involvement of complex I, reactive oxygen species and cardiolipin. Biochim Biophys Acta 1767:1260–1267

    Article  CAS  Google Scholar 

  • Schlame M, Rua D, Greenberg ML (2000) The biosynthesis and functional role of cardiolipin. Prog Lipid Res 39:257–288

    Article  CAS  Google Scholar 

  • Senatore V, Cione E, Gnoni A, Genchi G (2010) Retinoylation reactions are inversely related to the cardiolipin level in testes mitochondria from hypothyroid rats. J Bioenerg Biomembr 42:321–328

    Article  CAS  Google Scholar 

  • Siculella L, Sabetta S, Giudetti AM, Gnoni GV (2006) Hypothyroidism reduces tricarboxylate carrier activity and expression in rat liver mitochondria by reducing nuclear transcription rate and splicing efficiency. J Biol Chem 281:19072–19080

    Article  CAS  Google Scholar 

  • Taş S, Dirican M, Sarandöl E, Serdar Z (2006) The effect of taurine supplementation on oxidative stress in experimental hypothyroidism. Cell Biochem Funct 24:153–158

    Article  Google Scholar 

  • Venditti P, De Rosa R, Di Meo S (2003) Effect of thyroid state on H2O2 production by rat liver mitochondria. Mol Cell Endocrinol 205:185–192

    Article  CAS  Google Scholar 

  • Wratten ML, Van Ginkel G, Van AA, Veld T, Bekker A, Van Fassen EE, Sevanian A (1992) Structural and dynamic effect of oxidatively modified phospholipids in unsaturated lipid membranes. Biochemistry 31:10901–10907

    Article  CAS  Google Scholar 

  • Wrutniak-Cabello C, Casas F, Cabello G (2001) Thyroid hormone action in mitochondria. J Mol Endocrinol 26:67–77

    Article  CAS  Google Scholar 

  • Yilmaz S, Ozan S, Benzer F, Canatan H (2003) Oxidative damage and antioxidant enzyme activities in experimental hypothyroidism. Cell Biochem Funct 21:325–330

    Article  CAS  Google Scholar 

  • Zanotti F, Raho G, Gaballo A, Papa S (2004) Inhibitory and anchoring domains in the ATPase inhibitor protein IF1 of bovine heart mitochondrial ATP synthase. J Bioenerg Biomembr 36:447–457

    Article  CAS  Google Scholar 

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Correspondence to Gabriele Vincenzo Gnoni.

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Alessandro Cavallo and Antonio Gnoni contributed equally to this work

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Cavallo, A., Gnoni, A., Conte, E. et al. 3,5-Diiodo-L-Thyronine increases FoF1-ATP synthase activity and cardiolipin level in liver mitochondria of hypothyroid rats. J Bioenerg Biomembr 43, 349–357 (2011). https://doi.org/10.1007/s10863-011-9366-3

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  • DOI: https://doi.org/10.1007/s10863-011-9366-3

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