Mitochondrial-associated metabolic disorders: foundations, pathologies and recent progress

Nutrition & Metabolism

Joseph McInnes¹ 

[1] School of Engineering and Science, Research Center MOLIFE – Molecular Life Science, Jacobs University Bremen, Campus Ring 1, Research II, Room 120, Bremen D-28759, Germany

关键词: Disease;    Metabolism;    mtDNA;    Mitochondria;   

Others  :  803146
DOI  :  10.1186/1743-7075-10-63

 received in 2013-07-24, accepted in 2013-10-08,  发布年份 2013

【 摘 要 】

Research in the last decade has revolutionized the way in which we view mitochondria. Mitochondria are no longer viewed solely as cellular powerhouses; rather, mitochondria are now understood to be vibrant, mobile structures, constantly undergoing fusion and fission, and engaging in intimate interactions with other cellular compartments and structures. Findings have implicated mitochondria in a wide variety of cellular processes and molecular interactions, such as calcium buffering, lipid flux, and intracellular signaling. As such, it does not come as a surprise that an increasing number of human pathologies have been associated with functional defects in mitochondria. The difficulty in understanding and treating human pathologies caused by mitochondrial dysfunction arises from the complex relationships between mitochondria and other cellular processes, as well as the genetic background of such diseases. This review attempts to provide a summary of the background knowledge and recent developments in mitochondrial processes relating to mitochondrial-associated metabolic diseases arising from defects or deficiencies in mitochondrial function, as well as insights into current and future avenues for investigation.

【 授权许可】

   
2013 McInnes; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Ghisla S, Thorpe C: Acyl-CoA dehydrogenases. A mechanistic overview. Eur J Biochem 2004, 271:494-508.
• [2]Yang J, Staples O, Thomas LW, Briston T, Robson M, Poon E, Simões ML, El-Emir E, Buffa FM, Ahmed A, Annear NP, Shukla D, Pedley BR, Maxwell PH, Harris AL, Ashcroft M: Human CHCHD4 mitochondrial proteins regulate cellular oxygen consumption rate and metabolism and provide a critical role in hypoxia signaling and tumor progression. J Clin Invest 2012, 122:600-611.
• [3]Beavis AD: Upper and lower limits of the charge translocation stoichiometry of mitochondrial electron transport. J Biol Chem 1987, 262:6165-6173.
• [4]Nakamoto RK, Baylis Scanlon JA, Al-Shawi MK: The rotary mechanism of the ATP synthase. Arch Biochem Biophys 2008, 476:43-50.
• [5]Watt IN, Montgomery MG, Runswick MJ, Leslie AGW, Walker JE: Bioenergetic cost of making an adenosine triphosphate molecule in animal mitochondria. Proc Natl Acad Sci USA 2010, 107:16823-16827.
• [6]Kerner J, Hoppel C: Fatty acid import into mitochondria. Biochim Biophys Acta 2000, 1486:1-17.
• [7]Wanders RJA, Ruiter JPN, IJLst L, Waterham HR, Houten SM: The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results. J Inherit Metab Dis 2010, 33:479-494.
• [8]Westermann B: Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 2010, 11:872-884.
• [9]Chan DC: Fusion and fission: interlinked processes critical for mitochondrial health. Annu Rev Genet 2012, 46:265-287.
• [10]Chang C-R, Blackstone C: Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann N Y Acad Sci 2010, 1201:34-39.
• [11]Yoon Y, Krueger EW, Oswald BJ, McNiven MA: The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 2003, 23:5409-5420.
• [12]Otera H, Wang C, Cleland MM, Setoguchi K, Yokota S, Youle RJ, Mihara K: Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells. J Cell Biol 2010, 191:1141-1158.
• [13]Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK: ER tubules mark sites of mitochondrial division. Science 2011, 334:358-362.
• [14]Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel CP: Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 2000, 26:207-210.
• [15]Youle RJ, van der Bliek AM: Mitochondrial fission, fusion, and stress. Science 2012, 337:1062-1065.
• [16]Youle RJ, Narendra DP: Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011, 12:9-14.
• [17]McInnes J: Insights on altered mitochondrial function and dynamics in the pathogenesis of neurodegeneration. Transl Neurodegener 2013, 2:12. BioMed Central Full Text
• [18]Schweers RL, Zhang J, Randall MS, Loyd MR, Li W, Dorsey FC, Kundu M, Opferman JT, Cleveland JL, Miller JL, Ney PA: NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci USA 2007, 104:19500-19505.
• [19]Zhang J, Ney PA: NIX induces mitochondrial autophagy in reticulocytes. Autophagy 2008, 4:354-356.
• [20]Nunnari J, Suomalainen A: Mitochondria: in sickness and in health. Cell 2012, 148:1145-1159.
• [21]Gilkerson RW, De Vries RLA, Lebot P, Wikstrom JD, Torgyekes E, Shirihai OS, Przedborski S, Schon EA: Mitochondrial autophagy in cells with mtDNA mutations results from synergistic loss of transmembrane potential and mTORC1 inhibition. Hum Mol Genet 2012, 21:978-990.
• [22]Ding W-X, Yin X-M: Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem 2012, 393:547-564.
• [23]Ricchetti M, Fairhead C, Dujon B: Mitochondrial DNA repairs double-strand breaks in yeast chromosomes. Nature 1999, 402:96-100.
• [24]Wallace DC: Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci USA 1994, 91:8739-8746.
• [25]Lightowlers RN, Chinnery PF, Turnbull DM, Howell N: Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet 1997, 13:450-455.
• [26]Holt IJ: Zen and the art of mitochondrial DNA maintenance. Trends Genet 2010, 26:103-109.
• [27]Kazak L, Reyes A, Holt IJ: Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol 2012, 13:659-671.
• [28]Larsen NB, Rasmussen M, Rasmussen LJ: Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 2005, 5:89-108.
• [29]Szczesny B, Tann AW, Longley MJ, Copeland WC, Mitra S: Long patch base excision repair in mammalian mitochondrial genomes. J Biol Chem 2008, 283:26349-26356.
• [30]Kamenisch Y, Fousteri M, Knoch J, von A-K T, Fehrenbacher B, Kato H, Becker T, Dollé MET, Kuiper R, Majora M, Schaller M, van der Horst GTJ, van Steeg H, Röcken M, Rapaport D, Krutmann J, Mullenders LH, Berneburg M: Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging. J Exp Med 2010, 207:379-390.
• [31]Das BB, Dexheimer TS, Maddali K, Pommier Y: Role of tyrosyl-DNA phosphodiesterase (TDP1) in mitochondria. Proc Natl Acad Sci USA 2010, 107:19790-19795.
• [32]Thyagarajan B, Padua RA, Campbell C: Mammalian mitochondria possess homologous DNA recombination activity. J Biol Chem 1996, 271:27536-27543.
• [33]Bacman SR, Williams SL, Moraes CT: Intra- and inter-molecular recombination of mitochondrial DNA after in vivo induction of multiple double-strand breaks. Nucleic Acids Res 2009, 37:4218-4226.
• [34]Pavlov YI, Mian IM, Kunkel TA: Evidence for preferential mismatch repair of lagging strand DNA replication errors in yeast. Curr Biol 2003, 13:744-748.
• [35]Tann AW, Boldogh I, Meiss G, Qian W, Van Houten B, Mitra S, Szczesny B: Apoptosis induced by persistent single-strand breaks in mitochondrial genome: critical role of EXOG (5′-EXO/endonuclease) in their repair. J Biol Chem 2011, 286:31975-31983.
• [36]Johnson DT, Harris RA, French S, Blair PV, You J, Bemis KG, Wang M, Balaban RS: Tissue heterogeneity of the mammalian mitochondrial proteome. Am J Physiol Cell Physiol 2007, 292:C689-C697.
• [37]Arco AD, Satrústegui J: New mitochondrial carriers: an overview. Cell Mol Life Sci 2005, 62:2204-2227.
• [38]Covian R, Balaban RS: Cardiac mitochondrial matrix and respiratory complex protein phosphorylation. Am J Physiol Heart Circ Physiol 2012, 303:H940-H966.
• [39]Pizzo P, Drago I, Filadi R, Pozzan T: Mitochondrial Ca2+ homeostasis: mechanism, role, and tissue specificities. Pflugers Arch 2012, 464:3-17.
• [40]Swayne TC, Zhou C, Boldogh IR, Charalel JK, McFaline-Figueroa JR, Thoms S, Yang C, Leung G, McInnes J, Erdmann R, Pon LA: Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast. Curr Biol 2011, 21:1994-1999.
• [41]Rowland AA, Voeltz GK: Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol 2012, 13:607-625.
• [42]Osman C, Voelker DR, Langer T: Making heads or tails of phospholipids in mitochondria. J Cell Biol 2011, 192:7-16.
• [43]van Meer G, Voelker DR, Feigenson GW: Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 2008, 9:112-124.
• [44]de Brito OM, Scorrano L: Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 2008, 456:605-610.
• [45]Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T: Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 1998, 280:1763-1766.
• [46]Berridge MJ: The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 2002, 32:235-249.
• [47]Rizzuto R, De Stefani D, Raffaello A, Mammucari C: Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 2012, 13:566-578.
• [48]Bakowski D, Nelson C, Parekh AB: Endoplasmic reticulum-mitochondria coupling: local Ca2+ signalling with functional consequences. Pflugers Arch 2012, 464:27-32.
• [49]Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC: Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol. J Cell Biol 2003, 160:1115-1127.
• [50]Lebiedzinska M, Szabadkai G, Jones AWE, Duszynski J, Wieckowski MR: Interactions between the endoplasmic reticulum, mitochondria, plasma membrane and other subcellular organelles. Int J Biochem Cell Biol 2009, 41:1805-1816.
• [51]Kang H-C, Lee Y-M, Kim HD, Lee JS, Slama A: Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 2007, 48:82-88.
• [52]Santra S, Gilkerson RW, Davidson M, Schon EA: Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 2004, 56:662-669.
• [53]Ahola-Erkkilä S, Carroll CJ, Peltola-Mjösund K, Tulkki V, Mattila I, Seppänen-Laakso T, Oresic M, Tyynismaa H, Suomalainen A: Ketogenic diet slows down mitochondrial myopathy progression in mice. Hum Mol Genet 2010, 19:1974-1984.
• [54]Pichaud N, Messmer M, Correa CC, Ballard JWO: Diet influences the intake target and mitochondrial functions of Drosophila melanogaster males. Mitochondrion 2013. in press
• [55]Finsterer J, Zarrouk Mahjoub S: Epilepsy in mitochondrial disorders. Seizure 2012, 21:316-321.
• [56]Taivassalo T, Fu K, Johns T, Arnold D, Karpati G, Shoubridge EA: Gene shifting: a novel therapy for mitochondrial myopathy. Hum Mol Genet 1999, 8:1047-1052.
• [57]Chomyn A: The myoclonic epilepsy and ragged-red fiber mutation provides new insights into human mitochondrial function and genetics. Am J Hum Genet 1998, 62:745-751.
• [58]Chinnery PF, Johnson MA, Wardell TM, Singh-Kler R, Hayes C, Brown DT, Taylor RW, Bindoff LA, Turnbull DM: The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 2000, 48:188-193.
• [59]Cree LM, Samuels DC, de Sousa Lopes SC, Rajasimha HK, Wonnapinij P, Mann JR, Dahl H-HM, Chinnery PF: A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Nat Genet 2008, 40:249-254.
• [60]Pfeffer G, Chinnery PF: Diagnosis and treatment of mitochondrial myopathies. Ann Med 2013, 45:4-16.
• [61]Kraut JA, Madias NE: Metabolic acidosis: pathophysiology, diagnosis and management. Nat Publ Group 2010, 6:274-285.
• [62]Renda F, Mura P, Finco G, Ferrazin F, Pani L, Landoni G: Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review. Eur Rev Med Pharmacol Sci 2013, 17(Suppl 1):45-49.
• [63]Forsythe SM, Schmidt GA: Sodium bicarbonate for the treatment of lactic acidosis. Chest 2000, 117:260-267.
• [64]Luft FC: Lactic acidosis update for critical care clinicians. J Am Soc Nephrol 2001, 12(Suppl 17):S15-S19.
• [65]Pavlakis SG, Phillips PC, DiMauro S, De Vivo DC, Rowland LP: Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome. Ann Neurol 1984, 16:481-488.
• [66]Kirby DM, McFarland R, Ohtake A, Dunning C, Ryan MT, Wilson C, Ketteridge D, Turnbull DM, Thorburn DR, Taylor RW: Mutations of the mitochondrial ND1 gene as a cause of MELAS. J Med Genet 2004, 41:784-789.
• [67]Taylor RW, Turnbull DM: Mitochondrial DNA mutations in human disease. Nat Rev Genet 2005, 6:389-402.
• [68]Turunen M, Olsson J, Dallner G: Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004, 1660:171-199.
• [69]Hirano M, Garone C, Quinzii CM: CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders. Biochim Biophys Acta 1820, 2012:625-631.
• [70]Rahman S, Clarke CF, Hirano M: 176th ENMC International Workshop: diagnosis and treatment of coenzyme Q10 deficiency. 2012, 76-86. [Neuromuscul Disord, Volume 22]
• [71]Quinzii CM, Hirano M: Primary and secondary CoQ(10) deficiencies in humans. Biofactors 2011, 37:361-365.
• [72]Deodato F, Lucioli S, Rizzo C, Meschini MC, Santorelli FM, Bertini E, Dionisi-Vici C, Carrozzo R: Mitochondrial DNA depletion syndromes: an update. Paediatri Child Health 2009, 19:S32-S37.
• [73]Poulton J, Hirano M, Spinazzola A, Arenas Hernandez M, Jardel C, Lombès A, Czermin B, Horvath R, Taanman JW, Rotig A, Zeviani M, Fratter C: Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excluding the mitochondrial gamma polymerase, POLG1). Biochim Biophys Acta 2009, 1792:1109-1112.
• [74]Suomalainen A, Isohanni P: Mitochondrial DNA depletion syndromes–many genes, common mechanisms. Neuromuscul Disord 2010, 20:429-437.
• [75]Nishino I, Spinazzola A, Hirano M: Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 1999, 283:689-692.
• [76]Garone C, Tadesse S, Hirano M: Clinical and genetic spectrum of mitochondrial neurogastrointestinal encephalomyopathy. Brain 2011, 134:3326-3332.
• [77]Martí R, Spinazzola A, Tadesse S, Nishino I, Nishigaki Y, Hirano M: Definitive diagnosis of mitochondrial neurogastrointestinal encephalomyopathy by biochemical assays. Clin Chem 2004, 50:120-124.
• [78]Song S, Wheeler LJ, Mathews CK: Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA. J Biol Chem 2003, 278:43893-43896.
• [79]la Marca G, Malvagia S, Casetta B, Pasquini E, Pela I, Hirano M, Donati MA, Zammarchi E: Pre- and post-dialysis quantitative dosage of thymidine in urine and plasma of a MNGIE patient by using HPLC-ESI-MS/MS. J Mass Spectrom 2006, 41:586-592.
• [80]Lara MC, Weiss B, Illa I, Madoz P, Massuet L, Andreu AL, Valentino ML, Anikster Y, Hirano M, Martí R: Infusion of platelets transiently reduces nucleoside overload in MNGIE. Neurology 2006, 67:1461-1463.
• [81]Hudson G, Chinnery PF: Mitochondrial DNA polymerase-gamma and human disease. Hum Mol Genet 2006, 15(2):R244-R252.
• [82]Zhang L, Chan SSL, Wolff DJ: Mitochondrial disorders of DNA polymerase γ dysfunction: from anatomic to molecular pathology diagnosis. Arch Pathol Lab Med 2011, 135:925-934.
• [83]Hakonen AH, Isohanni P, Paetau A, Herva R, Suomalainen A, Lönnqvist T: Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain 2007, 130:3032-3040.
• [84]Chinnery PF, Zeviani M: 155th ENMC workshop: polymerase gamma and disorders of mitochondrial DNA synthesis, 21–23 September 2007, Naarden, The Netherlands. Neuromuscul Disord 2008, 18:259-267.
• [85]Cohen BH, Naviaux RK: The clinical diagnosis of POLG disease and other mitochondrial DNA depletion disorders. Methods 2010, 51:364-373.
• [86]Copeland WC: Defects in mitochondrial DNA replication and human disease. Crit Rev Biochem Mol Biol 2012, 47:64-74.
• [87]Chen L, Magliano DJ, Zimmet PZ: The worldwide epidemiology of type 2 diabetes mellitus–present and future perspectives. Nat Rev Endocrinol 2012, 8:228-236.
• [88]Boden G, Chen X, Ruiz J, White JV, Rossetti L: Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 1994, 93:2438-2446.
• [89]Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI: Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002, 277:50230-50236.
• [90]Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI: Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003, 300:1140-1142.
• [91]Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G: Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 1999, 286:774-779.
• [92]Kelley DE, He J, Menshikova EV, Ritov VB: Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002, 51:2944-2950.
• [93]Maassen JA, 'T Hart LM, Van Essen E, Heine RJ, Nijpels G, Jahangir Tafrechi RS, Raap AK, Janssen GMC, Lemkes HHPJ: Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 2004, 53(1):S103-S109.
• [94]van den Ouweland JM, Lemkes HH, Trembath RC, Ross R, Velho G, Cohen D, Froguel P, Maassen JA: Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes 1994, 43:746-751.
• [95]Lowell BB, Shulman GI: Mitochondrial dysfunction and type 2 diabetes. Science 2005, 307:384-387.
• [96]Patti M-E, Corvera S: The role of mitochondria in the pathogenesis of type 2 diabetes. Endocr Rev 2010, 31:364-395.
• [97]Chatterjee A, Dasgupta S, Sidransky D: Mitochondrial subversion in cancer. Canc Prev Res (Phila) 2011, 4:638-654.
• [98]Purdue MP, Hofmann JN, Colt JS, Hoxha M, Ruterbusch JJ, Davis FG, Rothman N, Wacholder S, Schwartz KL, Baccarelli A, Chow W-H: A case–control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma. PLoS ONE 2012, 7:e43149.
• [99]Lin C-S, Wang L-S, Tsai C-M, Wei Y-H: Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy. Interact Cardiovasc Thorac Surg 2008, 7:954-958.
• [100]Hosgood HD, Liu C-S, Rothman N, Weinstein SJ, Bonner MR, Shen M, Lim U, Virtamo J, Cheng W-L, Albanes D, Lan Q: Mitochondrial DNA copy number and lung cancer risk in a prospective cohort study. Carcinogenesis 2010, 31:847-849.
• [101]Yu M, Zhou Y, Shi Y, Ning L, Yang Y, Wei X, Zhang N, Hao X, Niu R: Reduced mitochondrial DNA copy number is correlated with tumor progression and prognosis in Chinese breast cancer patients. IUBMB Life 2007, 59:450-457.
• [102]Marchi S, Lupini L, Patergnani S, Rimessi A, Missiroli S, Bonora M, Bononi A, Corrà F, Giorgi C, De Marchi E, Poletti F, Gafà R, Lanza G, Negrini M, Rizzuto R, Pinton P: Downregulation of the Mitochondrial Calcium Uniporter by Cancer-Related miR-25. Curr Biol 2012, 23:58-63.
• [103]Sripada L, Tomar D, Singh R: Mitochondria: one of the destinations of miRNAs. Mitochondrion 2012, 12:593-599.
• [104]Bienertova-Vasku J, Sana J, Slaby O: The role of microRNAs in mitochondria in cancer. Canc Lett 2013, 336:1-7.
• [105]Rosca MG, Hoppel CL: Mitochondria in heart failure. Cardiovasc Res 2010, 88:40-50.
• [106]Stanley WC, Hoppel CL: Mitochondrial dysfunction in heart failure: potential for therapeutic interventions? Cardiovasc Res 2000, 45:805-806.
• [107]Jarreta D, Orús J, Barrientos A, Miró O, Roig E, Heras M, Moraes CT, Cardellach F, Casademont J: Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy. Cardiovasc Res 2000, 45:860-865.
• [108]Guzy RD, Hoyos B, Robin E, Chen H, Liu L, Mansfield KD, Simon MC, Hammerling U, Schumacker PT: Mitochondrial complex III is required for hypoxia-induced ROS production and cellular oxygen sensing. Cell Metab 2005, 1:401-408.
• [109]Murray AJ, Edwards LM, Clarke K: Mitochondria and heart failure. Curr Opin Clin Nutr Metab Care 2007, 10:704-711.
• [110]Smith RAJ, Murphy MP: Mitochondria-targeted antioxidants as therapies. Discov Med 2011, 11:106-114.
• [111]Markovets AM, Fursova AZ, Kolosova NG: Therapeutic action of the mitochondria-targeted antioxidant SkQ1 on retinopathy in OXYS rats linked with improvement of VEGF and PEDF gene expression. PLoS ONE 2011, 6:e21682.
• [112]Bolisetty S, Traylor A, Zarjou A, Johnson MS, Benavides GA, Ricart K, Boddu R, Moore RD, Landar A, Barnes S, Darley-Usmar V, Agarwal A: Mitochondria-targeted heme oxygenase-1 decreases oxidative stress in renal epithelial cells. Am J Physiol Renal Physiol 2013, 305:F255-F264.
• [113]Bayeva M, Gheorghiade M, Ardehali H: Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol 2013, 61:599-610.
• [114]Schon EA, DiMauro S, Hirano M, Gilkerson RW: Therapeutic prospects for mitochondrial disease. Trends Mol Med 2010, 16:268-276.
• [115]Suomalainen A: Therapy for mitochondrial disorders: little proof, high research activity, some promise. Semin Fetal Neonatal Med 2011, 16:236-240.