Generic placeholder image

Current Protein & Peptide Science


ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

Review Article

Mitochondrial Dysfunction in Skeletal Muscle Pathologies

Author(s): Johanna Abrigo, Felipe Simon, Daniel Cabrera, Cristian Vilos and Claudio Cabello-Verrugio*

Volume 20, Issue 6, 2019

Page: [536 - 546] Pages: 11

DOI: 10.2174/1389203720666190402100902

Price: $65


Several molecular mechanisms are involved in the regulation of skeletal muscle function. Among them, mitochondrial activity can be identified. The mitochondria is an important and essential organelle in the skeletal muscle that is involved in metabolic regulation and ATP production, which are two key elements of muscle contractibility and plasticity. Thus, in this review, we present the critical and recent antecedents regarding the mechanisms through which mitochondrial dysfunction can be involved in the generation and development of skeletal muscle pathologies, its contribution to detrimental functioning in skeletal muscle and its crosstalk with other typical signaling pathways related to muscle diseases. In addition, an update on the development of new strategies with therapeutic potential to inhibit the deleterious impact of mitochondrial dysfunction in skeletal muscle is discussed.

Keywords: Mitochondria, ROS, skeletal muscle, atrophy, dystrophy, ATP production.

Graphical Abstract
Damas, F.; Libardi, C.A.; Ugrinowitsch, C. The development of skeletal muscle hypertrophy through resistance training: The role of muscle damage and muscle protein synthesis. Eur. J. Appl. Physiol., 2018, 118(3), 485-500.
Wallace, D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu. Rev. Genet., 2005, 39, 359-407.
Zurlo, F.; Larson, K.; Bogardus, C.; Ravussin, E. Skeletal muscle metabolism is a major determinant of resting energy expenditure. J. Clin. Invest., 1990, 86(5), 1423-1427.
Weibel, E.R.; Hoppeler, H. Exercise-induced maximal metabolic rate scales with muscle aerobic capacity. J. Exp. Biol., 2005, 208(Pt 9), 1635-1644.
Fealy, C.E.; Mulya, A.; Axelrod, C.L.; Kirwan, J.P. Mitochondrial dynamics in skeletal muscle insulin resistance and type 2 diabetes. Transl. Res., 2018, 202, 69-82.
Pejznochova, M.; Tesarova, M.; Hansikova, H.; Magner, M.; Honzik, T.; Vinsova, K.; Hajkova, Z.; Havlickova, V.; Zeman, J. Mitochondrial DNA content and expression of genes involved in mtDNA transcription, regulation and maintenance during human fetal development. Mitochondrion, 2010, 10(4), 321-329.
Ashrafi, G.; Schwarz, T.L. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ., 2013, 20(1), 31-42.
Hood, D.A. Invited review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle. J. Appl. Physiol., 2001, 90(3), 1137-1157.
Iqbal, S.; Ostojic, O.; Singh, K.; Joseph, A.M.; Hood, D.A. Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse. Muscle Nerve, 2013, 48(6), 963-970.
Wasilewski, M.; Scorrano, L. The changing shape of mitochondrial apoptosis. Trends Endocrinol. Metab., 2009, 20(6), 287-294.
Arnoult, D. Mitochondrial fragmentation in apoptosis. Trends Cell Biol., 2007, 17(1), 6-12.
Laporte, C.; Kosta, A.; Klein, G.; Aubry, L.; Lam, D.; Tresse, E.; Luciani, M.F.; Golstein, P. A necrotic cell death model in a protist. Cell Death Differ., 2007, 14(2), 266-274.
Liu, X.; Hajnoczky, G. Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ., 2011, 18(10), 1561-1572.
Detmer, S.A.; Chan, D.C. Functions and dysfunctions of mitochondrial dynamics. Nat. Rev. Mol. Cell Biol., 2007, 8(11), 870-879.
Kwong, J.Q.; Molkentin, J.D. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metab., 2015, 21(2), 206-214.
Mishra, N.; Kar, R.; Singha, P.K.; Venkatachalam, M.A.; McEwen, D.G.; Saikumar, P. Inhibition of mitochondrial division through covalent modification of Drp1 protein by 15 deoxy-Delta(12,14)-prostaglandin J2. Biochem. Biophys. Res. Commun., 2010, 395(1), 17-24.
Palmer, C.S.; Osellame, L.D.; Laine, D.; Koutsopoulos, O.S.; Frazier, A.E.; Ryan, M.T. MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep., 2011, 12(6), 565-573.
Lazarou, M.; Sliter, D.A.; Kane, L.A.; Sarraf, S.A.; Wang, C.; Burman, J.L.; Sideris, D.P.; Fogel, A.I.; Youle, R.J. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature, 2015, 524(7565), 309-314.
Twig, G.; Elorza, A.; Molina, A.J.; Mohamed, H.; Wikstrom, J.D.; Walzer, G.; Stiles, L.; Haigh, S.E.; Katz, S.; Las, G.; Alroy, J.; Wu, M.; Py, B.F.; Yuan, J.; Deeney, J.T.; Corkey, B.E.; Shirihai, O.S. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J., 2008, 27(2), 433-446.
Qi, Y.; Yan, L.; Yu, C.; Guo, X.; Zhou, X.; Hu, X.; Huang, X.; Rao, Z.; Lou, Z.; Hu, J. Structures of human mitofusin 1 provide insight into mitochondrial tethering. J. Cell Biol., 2016, 215(5), 621-629.
MacVicar, T.; Langer, T. OPA1 processing in cell death and disease - the long and short of it. J. Cell Sci., 2016, 129(12), 2297-2306.
Chakrabarty, S.; Kabekkodu, S.P.; Singh, R.P.; Thangaraj, K.; Singh, K.K.; Satyamoorthy, K. Mitochondria in health and disease. Mitochondrion, 2018, 43, 25-29.
Chen, H.; Vermulst, M.; Wang, Y.E.; Chomyn, A.; Prolla, T.A.; McCaffery, J.M.; Chan, D.C. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell, 2010, 141(2), 280-289.
Lee, I.H.; Finkel, T. Metabolic regulation of the cell cycle. Curr. Opin. Cell Biol., 2013, 25(6), 724-729.
Salazar-Roa, M.; Malumbres, M. Fueling the cell division cycle. Trends Cell Biol., 2017, 27(1), 69-81.
Romanello, V.; Sandri, M. Mitochondrial biogenesis and fragmentation as regulators of protein degradation in striated muscles. J. Mol. Cell. Cardiol., 2013, 55, 64-72.
Bonaldo, P.; Sandri, M. Cellular and molecular mechanisms of muscle atrophy. Dis. Model. Mech., 2013, 6(1), 25-39.
Jackman, R.W.; Kandarian, S.C. The molecular basis of skeletal muscle atrophy. Am. J. Physiol. Cell Physiol., 2004. 287(4), C834 C843.
Fanzani, A.; Conraads, V.M.; Penna, F.; Martinet, W. Molecular and cellular mechanisms of skeletal muscle atrophy: An update. J. Cachexia Sarcopenia Muscle, 2012, 3(3), 163-179.
Frontera, W.R.; Zayas, A.R.; Rodriguez, N. Aging of human muscle: Understanding sarcopenia at the single muscle cell level. Phys. Med. Rehabil. Clin. N. Am., 2012, 23(1), 201-207. [xiii.].
Miljkovic, N.; Lim, J.Y.; Miljkovic, I.; Frontera, W.R. Aging of skeletal muscle fibers. Ann. Rehabil. Med., 2015, 39(2), 155-162.
Vinciguerra, M.; Musaro, A.; Rosenthal, N. Regulation of muscle atrophy in aging and disease. Adv. Exp. Med. Biol., 2010, 694, 211-233.
Bongers, K.S.; Fox, D.K.; Ebert, S.M.; Kunkel, S.D.; Dyle, M.C.; Bullard, S.A.; Dierdorff, J.M.; Adams, C.M. Skeletal muscle denervation causes skeletal muscle atrophy through a pathway that involves both Gadd45a and HDAC4. Am. J. Physiol. Endocrinol. Metab., 2013, 305(7), E907-E915.
Bodine, S.C. Disuse-induced muscle wasting. Int. J. Biochem. Cell Biol., 2013, 45(10), 2200-2208.
Ebner, N.; Sliziuk, V.; Scherbakov, N.; Sandek, A. Muscle wasting in ageing and chronic illness. ESC Heart Fail., 2015, 2(2), 58-68.
Nathan, J.; Fuld, J. Skeletal muscle dysfunction: A ubiquitous outcome in chronic disease? Thorax, 2010, 65(2), 97-98.
Dhanapal, R.; Saraswathi, T.; Govind, R.N. Cancer cachexia. J. Oral Maxillofac. Pathol., 2011, 15(3), 257-260.
Barreiro, E.; Jaitovich, A. Muscle atrophy in chronic obstructive pulmonary disease: Molecular basis and potential therapeutic targets. J. Thorac. Dis., 2018, 10(Suppl. 12), S1415-S1424.
Campos, F.; Abrigo, J.; Aguirre, F.; Garces, B.; Arrese, M.; Karpen, S.; Cabrera, D.; Andia, M.E.; Simon, F.; Cabello-Verrugio, C. Sarcopenia in a mice model of chronic liver disease: Role of the ubiquitin-proteasome system and oxidative stress. Pflugers Arch., 2018, 470(10), 1503-1519.
Dasarathy, S. Cause and management of muscle wasting in chronic liver disease. Curr. Opin. Gastroenterol., 2016, 32(3), 159-165.
von Haehling, S.; Ebner, N.; Dos Santos, M.R.; Springer, J.; Anker, S.D. Muscle wasting and cachexia in heart failure: Mechanisms and therapies. Nat. Rev. Cardiol., 2017, 14(6), 323-341.
Doehner, W.; Turhan, G.; Leyva, F.; Rauchhaus, M.; Sandek, A.; Jankowska, E.A.; von Haehling, S.; Anker, S.D. Skeletal muscle weakness is related to insulin resistance in patients with chronic heart failure. ESC Heart Fail., 2015, 2(2), 85-89.
Perry, B.D.; Caldow, M.K.; Brennan-Speranza, T.C.; Sbaraglia, M.; Jerums, G.; Garnham, A.; Wong, C.; Levinger, P.; Asrar Ul Haq, M.; Hare, D.L.; Price, S.R.; Levinger, I. Muscle atrophy in patients with Type 2 Diabetes Mellitus: Roles of inflammatory pathways, physical activity and exercise. Exerc. Immunol. Rev., 2016, 22, 94-109.
Sishi, B.; Loos, B.; Ellis, B.; Smith, W.; du Toit, E.F.; Engelbrecht, A.M. Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model. Exp. Physiol., 2011, 96(2), 179-193.
De Palma, C.; Perrotta, C.; Pellegrino, P.; Clementi, E.; Cervia, D. Skeletal muscle homeostasis in duchenne muscular dystrophy: Modulating autophagy as a promising therapeutic strategy. Front. Aging Neurosci., 2014, 6, 188.
Zielonka, D.; Piotrowska, I.; Marcinkowski, J.T.; Mielcarek, M. Skeletal muscle pathology in Huntington’s disease. Front. Physiol., 2014, 5, 380.
Takagi, D.; Hirano, H.; Watanabe, Y.; Edahiro, A.; Ohara, Y.; Yoshida, H.; Kim, H.; Murakami, K.; Hironaka, S. Relationship between skeletal muscle mass and swallowing function in patients with Alzheimer’s disease. Geriatr. Gerontol. Int., 2017, 17(3), 402-409.
Bialek, P.; Morris, C.; Parkington, J.; St Andre, M.; Owens, J.; Yaworsky, P.; Seeherman, H.; Jelinsky, S.A. Distinct protein degradation profiles are induced by different disuse models of skeletal muscle atrophy. Physiol. Genomics, 2011, 43(19), 1075-1086.
Lee, S.W.; Dai, G.; Hu, Z.; Wang, X.; Du, J.; Mitch, W.E. Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin-proteasome systems by phosphatidy-linositol 3 kinase. J. Am. Soc. Nephrol., 2004, 15(6), 1537-1545.
Sandri, M. Protein breakdown in muscle wasting: Role of autophagy-lysosome and ubiquitin-proteasome. Int. J. Biochem. Cell Biol., 2013, 45(10), 2121-2129.
Roos, M.R.; Rice, C.L.; Vandervoort, A.A. Age-related changes in motor unit function. Muscle Nerve, 1997, 20(6), 679-690.
Visser, M.; Deeg, D.J.; Lips, P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): The Longitudinal Aging Study Amsterdam. J. Clin. Endocrinol. Metab., 2003, 88(12), 5766-5772.
Gallegly, J.C.; Turesky, N.A.; Strotman, B.A.; Gurley, C.M.; Peterson, C.A.; Dupont-Versteegden, E.E. Satellite cell regulation of muscle mass is altered at old age. J. Appl. Physiol., 2004, 97(3), 1082-1090.
Dupont-Versteegden, E.E. Apoptosis in muscle atrophy: Relevance to sarcopenia. Exp. Gerontol., 2005, 40(6), 473-481.
Cheema, N.; Herbst, A.; McKenzie, D.; Aiken, J.M. Apoptosis and necrosis mediate skeletal muscle fiber loss in age-induced mitochondrial enzymatic abnormalities. Aging Cell, 2015, 14(6), 1085-1093.
Bratic, A.; Larsson, N.G. The role of mitochondria in aging. J. Clin. Invest., 2013, 123(3), 951-957.
Wanagat, J.; Cao, Z.; Pathare, P.; Aiken, J.M. Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia. FASEB J., 2001, 15(2), 322-332.
Cao, Z.; Wanagat, J.; McKiernan, S.H.; Aiken, J.M. Mitochondrial DNA deletion mutations are concomitant with ragged red regions of individual, aged muscle fibers: Analysis by laser-capture microdissection. Nucleic Acids Res., 2001, 29(21), 4502-4508.
Lee, C.M.; Eimon, P.; Weindruch, R.; Aiken, J.M. Direct repeat sequences are not required at the breakpoints of age-associated mitochondrial DNA deletions in rhesus monkeys. Mech. Ageing Dev., 1994, 75(1), 69-79.
Bua, E.; Johnson, J.; Herbst, A.; Delong, B.; McKenzie, D.; Salamat, S.; Aiken, J.M. Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers. Am. J. Hum. Genet., 2006, 79(3), 469-480.
Chabi, B.; Ljubicic, V.; Menzies, K.J.; Huang, J.H.; Saleem, A.; Hood, D.A. Mitochondrial function and apoptotic susceptibility in aging skeletal muscle. Aging Cell, 2008, 7(1), 2-12.
Dirks, A.; Leeuwenburgh, C. Apoptosis in skeletal muscle with aging. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2002, 282(2), R519-R527.
Pistilli, E.E.; Siu, P.M.; Alway, S.E. Molecular regulation of apoptosis in fast plantaris muscles of aged rats. J. Gerontol. A Biol. Sci. Med. Sci., 2006, 61(3), 245-255.
Muller, F.L.; Song, W.; Jang, Y.C.; Liu, Y.; Sabia, M.; Richardson, A.; Van Remmen, H. Denervation-induced skeletal muscle atrophy is associated with increased mitochondrial ROS production. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2007, 293(3), R1159-R1168.
Spendiff, S.; Vuda, M.; Gouspillou, G.; Aare, S.; Perez, A.; Morais, J.A.; Jagoe, R.T.; Filion, M.E.; Glicksman, R.; Kapchinsky, S.; MacMillan, N.J.; Pion, C.H.; Aubertin-Leheudre, M.; Hettwer, S.; Correa, J.A.; Taivassalo, T.; Hepple, R.T. Denervation drives mitochondrial dysfunction in skeletal muscle of octogenarians. J. Physiol., 2016, 594(24), 7361-7379.
Powers, S.K.; Wiggs, M.P.; Duarte, J.A.; Zergeroglu, A.M.; Demirel, H.A. Mitochondrial signaling contributes to disuse muscle atrophy. Am. J. Physiol. Endocrinol. Metab., 2012, 303(1), E31-E39.
Tryon, L.D.; Vainshtein, A.; Memme, J.M.; Crilly, M.J.; Hood, D.A. Recent advances in mitochondrial turnover during chronic muscle disuse. Integr. Med. Res., 2014, 3(4), 161-171.
Gosker, H.R.; Hesselink, M.K.; Duimel, H.; Ward, K.A.; Schols, A.M. Reduced mitochondrial density in the vastus lateralis muscle of patients with COPD. Eur. Respir. J., 2007, 30(1), 73-79.
Picard, M.; Godin, R.; Sinnreich, M.; Baril, J.; Bourbeau, J.; Perrault, H.; Taivassalo, T.; Burelle, Y. The mitochondrial phenotype of peripheral muscle in chronic obstructive pulmonary disease: Disuse or dysfunction? Am. J. Respir. Crit. Care Med., 2008, 178(10), 1040-1047.
Bronstad, E.; Rognmo, O.; Tjonna, A.E.; Dedichen, H.H.; Kirkeby-Garstad, I.; Haberg, A.K.; Ingul, C.B.; Wisloff, U.; Steinshamn, S. High-intensity knee extensor training restores skeletal muscle function in COPD patients. Eur. Respir. J., 2012, 40(5), 1130-1136.
Naimi, A.I.; Bourbeau, J.; Perrault, H.; Baril, J.; Wright-Paradis, C.; Rossi, A.; Taivassalo, T.; Sheel, A.W.; Rabol, R.; Dela, F.; Boushel, R. Altered mitochondrial regulation in quadriceps muscles of patients with COPD. Clin. Physiol. Funct. Imaging, 2011, 31(2), 124-131.
Puente-Maestu, L.; Perez-Parra, J.; Godoy, R.; Moreno, N.; Tejedor, A.; Gonzalez-Aragoneses, F.; Bravo, J.L.; Alvarez, F.V.; Camano, S.; Agusti, A. Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients. Eur. Respir. J., 2009, 33(5), 1045-1052.
Rabinovich, R.A.; Bastos, R.; Ardite, E.; Llinas, L.; Orozco-Levi, M.; Gea, J.; Vilaro, J.; Barbera, J.A.; Rodriguez-Roisin, R.; Fernandez-Checa, J.C.; Roca, J. Mitochondrial dysfunction in COPD patients with low body mass index. Eur. Respir. J., 2007, 29(4), 643-650.
Taivassalo, T.; Hussain, S.N. Contribution of the mitochondria to locomotor muscle dysfunction in patients with COPD. Chest, 2016, 149(5), 1302-1312.
Agusti, A.G.; Sauleda, J.; Miralles, C.; Gomez, C.; Togores, B.; Sala, E.; Batle, S.; Busquets, X. Skeletal muscle apoptosis and weight loss in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2002, 166(4), 485-489.
Guo, Y.; Gosker, H.R.; Schols, A.M.; Kapchinsky, S.; Bourbeau, J.; Sandri, M.; Jagoe, R.T.; Debigare, R.; Maltais, F.; Taivassalo, T.; Hussain, S.N. Autophagy in locomotor muscles of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2013, 188(11), 1313-1320.
Brown, J.L.; Rosa-Caldwell, M.E.; Lee, D.E.; Blackwell, T.A.; Brown, L.A.; Perry, R.A.; Haynie, W.S.; Hardee, J.P.; Carson, J.A.; Wiggs, M.P.; Washington, T.A.; Greene, N.P. Mitochondrial degeneration precedes the development of muscle atrophy in progression of cancer cachexia in tumour-bearing mice. J. Cachexia Sarcopenia Muscle, 2017, 8(6), 926-938.
VanderVeen, B.N.; Fix, D.K.; Carson, J.A. Disrupted skeletal muscle mitochondrial dynamics, mitophagy, and biogenesis during cancer cachexia: A role for inflammation. Oxid. Med. Cell. Longev., 2017, 2017, 3292087.
Guido, C.; Whitaker-Menezes, D.; Lin, Z.; Pestell, R.G.; Howell, A.; Zimmers, T.A.; Casimiro, M.C.; Aquila, S.; Ando, S.; Martinez-Outschoorn, U.E.; Sotgia, F.; Lisanti, M.P. Mitochondrial fission induces glycolytic reprogramming in cancer-associated myofibroblasts, driving stromal lactate production, and early tumor growth. Oncotarget, 2012, 3(8), 798-810.
Marzetti, E.; Lorenzi, M.; Landi, F.; Picca, A.; Rosa, F.; Tanganelli, F.; Galli, M.; Doglietto, G.B.; Pacelli, F.; Cesari, M.; Bernabei, R.; Calvani, R.; Bossola, M. Altered mitochondrial quality control signaling in muscle of old gastric cancer patients with cachexia. Exp. Gerontol.,., 2017. 87(Pt A), 92-99.
White, J.P.; Puppa, M.J.; Sato, S.; Gao, S.; Price, R.L.; Baynes, J.W.; Kostek, M.C.; Matesic, L.E.; Carson, J.A. IL-6 regulation on skeletal muscle mitochondrial remodeling during cancer cachexia in the ApcMin/+ mouse. Skelet. Muscle, 2012, 2, 14.
Remels, A.H.; Gosker, H.R.; Schrauwen, P.; Hommelberg, P.P.; Sliwinski, P.; Polkey, M.; Galdiz, J.; Wouters, E.F.; Langen, R.C.; Schols, A.M. TNF-alpha impairs regulation of muscle oxidative phenotype: Implications for cachexia? FASEB J., 2010, 24(12), 5052-5062.
McLean, J.B.; Moylan, J.S.; Andrade, F.H. Mitochondria dysfunction in lung cancer-induced muscle wasting in C2C12 myotubes. Front. Physiol., 2014, 5, 503.
Debashree, B.; Kumar, M.; Keshava Prasad, T.S.; Natarajan, A.; Christopher, R.; Nalini, A.; Bindu, P.S.; Gayathri, N.; Srinivas Bharath, M.M. Mitochondrial dysfunction in human skeletal muscle biopsies of lipid storage disorder. J. Neurochem., 2018, 145(4), 323-341.
Dumas, J.F.; Simard, G.; Flamment, M.; Ducluzeau, P.H.; Ritz, P. Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans? Diabetes Metab., 2009, 35(3), 159-167.
Lowell, B.B.; Shulman, G.I. Mitochondrial dysfunction and type 2 diabetes. Science, 2005, 307(5708), 384-387.
Sreekumar, R.; Nair, K.S. Skeletal muscle mitochondrial dysfunction & diabetes. Indian J. Med. Res., 2007, 125(3), 399-410.
Xiao, Y.; Karam, C.; Yi, J.; Zhang, L.; Li, X.; Yoon, D.; Wang, H.; Dhakal, K.; Ramlow, P.; Yu, T.; Mo, Z.; Ma, J.; Zhou, J. ROS-related mitochondrial dysfunction in skeletal muscle of an ALS mouse model during the disease progression. Pharmacol. Res., 2018, 138, 25-36.
Gusella, J.F.; MacDonald, M.E.; Ambrose, C.M.; Duyao, M.P. Molecular genetics of Huntington’s disease. Arch. Neurol., 1993, 50(11), 1157-1163.
Busse, M.E.; Hughes, G.; Wiles, C.M.; Rosser, A.E. Use of hand-held dynamometry in the evaluation of lower limb muscle strength in people with Huntington’s disease. J. Neurol., 2008, 255(10), 1534-1540.
Reddy, P.H. Increased mitochondrial fission and neuronal dysfunction in Huntington’s disease: Implications for molecular inhibitors of excessive mitochondrial fission. Drug Discov. Today, 2014, 19(7), 951-955.
Cui, L.; Jeong, H.; Borovecki, F.; Parkhurst, C.N.; Tanese, N.; Krainc, D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neuro-degeneration. Cell, 2006, 127(1), 59-69.
Milakovic, T.; Johnson, G.V. Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin. J. Biol. Chem., 2005, 280(35), 30773-30782.
Panov, A.V.; Gutekunst, C.A.; Leavitt, B.R.; Hayden, M.R.; Burke, J.R.; Strittmatter, W.J.; Greenamyre, J.T. Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat. Neurosci., 2002, 5(8), 731-736.
Chaturvedi, R.K.; Adhihetty, P.; Shukla, S.; Hennessy, T.; Calingasan, N.; Yang, L.; Starkov, A.; Kiaei, M.; Cannella, M.; Sassone, J.; Ciammola, A.; Squitieri, F.; Beal, M.F. Impaired PGC-1alpha function in muscle in Huntington’s disease. Hum. Mol. Genet., 2009, 18(16), 3048-3065.
Lodi, R.; Schapira, A.H.; Manners, D.; Styles, P.; Wood, N.W.; Taylor, D.J.; Warner, T.T. Abnormal in vivo skeletal muscle energy metabolism in Huntington’s disease and dentatorubropallidoluysian atrophy. Ann. Neurol., 2000, 48(1), 72-76.
Saft, C.; Zange, J.; Andrich, J.; Muller, K.; Lindenberg, K.; Landwehrmeyer, B.; Vorgerd, M.; Kraus, P.H.; Przuntek, H.; Schols, L. Mitochondrial impairment in patients and asymptomatic mutation carriers of Huntington’s disease. Mov. Disord., 2005, 20(6), 674-679.
Ciammola, A.; Sassone, J.; Alberti, L.; Meola, G.; Mancinelli, E.; Russo, M.A.; Squitieri, F.; Silani, V. Increased apoptosis, Huntingtin inclusions and altered differentiation in muscle cell cultures from Huntington’s disease subjects. Cell Death Differ., 2006, 13(12), 2068-2078.
Ciammola, A.; Sassone, J.; Sciacco, M.; Mencacci, N.E.; Ripolone, M.; Bizzi, C.; Colciago, C.; Moggio, M.; Parati, G.; Silani, V.; Malfatto, G. Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington’s disease. Mov. Disord., 2011, 26(1), 130-137.
Cole, M.A.; Rafael, J.A.; Taylor, D.J.; Lodi, R.; Davies, K.E.; Styles, P. A quantitative study of bioenergetics in skeletal muscle lacking utrophin and dystrophin. Neuromuscul. Disord., 2002, 12(3), 247-257.
Hoffman, E.P.; Brown, R.H., Jr; Kunkel, L.M. Dystrophin: The protein product of the Duchenne muscular dystrophy locus. Cell, 1987, 51(6), 919-928.
Dunn, J.F.; Radda, G.K. Total ion content of skeletal and cardiac muscle in the mdx mouse dystrophy: Ca2+ is elevated at all ages. J. Neurol. Sci., 1991, 103(2), 226-231.
Percival, J.M.; Siegel, M.P.; Knowels, G.; Marcinek, D.J. Defects in mitochondrial localization and ATP synthesis in the mdx mouse model of Duchenne muscular dystrophy are not alleviated by PDE5 inhibition. Hum. Mol. Genet., 2013, 22(1), 153-167.
Rybalka, E.; Timpani, C.A.; Cooke, M.B.; Williams, A.D.; Hayes, A. Defects in mitochondrial ATP synthesis in dystrophin-deficient mdx skeletal muscles may be caused by complex I insufficiency. PLoS One, 2014, 9(12), e115763.
Rock, K.L.; Gramm, C.; Rothstein, L.; Clark, K.; Stein, R.; Dick, L.; Hwang, D.; Goldberg, A.L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell, 1994, 78(5), 761-771.
Lecker, S.H.; Goldberg, A.L.; Mitch, W.E. Protein degradation by the ubiquitin-proteasome pathway in normal and disease states. J. Am. Soc. Nephrol., 2006, 17(7), 1807-1819.
Murton, A.J.; Constantin, D.; Greenhaff, P.L. The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy. Biochim. Biophys. Acta, 2008, 1782(12), 730-743.
Lokireddy, S.; Wijesoma, I.W.; Sze, S.K.; McFarlane, C.; Kambadur, R.; Sharma, M. Identification of atrogin-1-targeted proteins during the myostatin-induced skeletal muscle wasting. Am. J. Physiol. Cell Physiol., 2012, 303(5), C512-C529.
Bragoszewski, P.; Gornicka, A.; Sztolsztener, M.E.; Chacinska, A. The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins. Mol. Cell. Biol., 2013, 33(11), 2136-2148.
Neutzner, A.; Youle, R.J.; Karbowski, M. Outer mitochondrial membrane protein degradation by the proteasome.Novartis Found Symp.,, 2007. , 287, 4-14; 14-20
Romanello, V.; Guadagnin, E.; Gomes, L.; Roder, I.; Sandri, C.; Petersen, Y.; Milan, G.; Masiero, E.; Del Piccolo, P.; Foretz, M.; Scorrano, L.; Rudolf, R.; Sandri, M. Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J., 2010, 29(10), 1774-1785.
Taylor, E.B.; Rutter, J. Mitochondrial quality control by the ubiquitin-proteasome system. Biochem. Soc. Trans., 2011, 39(5), 1509-1513.
Lehmann, G.; Udasin, R.G.; Ciechanover, A. On the linkage between the ubiquitin-proteasome system and the mitochondria. Biochem. Biophys. Res. Commun., 2016, 473(1), 80-86.
Balaban, R.S.; Nemoto, S.; Finkel, T. Mitochondria, oxidants, and aging. Cell, 2005, 120(4), 483-495.
Droge, W. Free radicals in the physiological control of cell function. Physiol. Rev., 2002, 82(1), 47-95.
Turrens, J.F. Mitochondrial formation of reactive oxygen species. J. Physiol., 2003, 552(Pt 2), 335-344.
Stowe, D.F.; Aldakkak, M.; Camara, A.K.; Riess, M.L.; Heinen, A.; Varadarajan, S.G.; Jiang, M.T. Cardiac mitochondrial preconditioning by Big Ca2+-sensitive K+ channel opening requires superoxide radical generation. Am. J. Physiol. Heart Circ. Physiol., 2006, 290(1), H434-H440.
Rahman, M.; Mofarrahi, M.; Kristof, A.S.; Nkengfac, B.; Harel, S.; Hussain, S.N. Reactive oxygen species regulation of autophagy in skeletal muscles. Antioxid. Redox Signal., 2014, 20(3), 443-459.
O’Leary, M.F.; Hood, D.A. Denervation-induced oxidative stress and autophagy signaling in muscle. Autophagy, 2009, 5(2), 230-231.
Sakellariou, G.K.; Pearson, T.; Lightfoot, A.P.; Nye, G.A.; Wells, N. Giakoumaki, II; Vasilaki, A.; Griffiths, R.D.; Jackson, M.J.; McArdle, A. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy. Sci. Rep., 2016, 6, 33944.
Bonnard, C.; Durand, A.; Peyrol, S.; Chanseaume, E.; Chauvin, M.A.; Morio, B.; Vidal, H.; Rieusset, J. Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J. Clin. Invest., 2008, 118(2), 789-800.
Brookes, P.S.; Yoon, Y.; Robotham, J.L.; Anders, M.W.; Sheu, S.S. Calcium, ATP, and ROS: A mitochondrial love-hate triangle. Am. J. Physiol. Cell Physiol., 2004, 287(4), C817-C833.
Fang, H.; Chen, M.; Ding, Y.; Shang, W.; Xu, J.; Zhang, X.; Zhang, W.; Li, K.; Xiao, Y.; Gao, F.; Shang, S.; Li, J.C.; Tian, X.L.; Wang, S.Q.; Zhou, J.; Weisleder, N.; Ma, J.; Ouyang, K.; Chen, J.; Wang, X.; Zheng, M.; Wang, W.; Zhang, X.; Cheng, H. Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Res., 2011, 21(9), 1295-1304.
Karam, C.; Yi, J.; Xiao, Y.; Dhakal, K.; Zhang, L.; Li, X.; Manno, C.; Xu, J.; Li, K.; Cheng, H.; Ma, J.; Zhou, J. Absence of physiological Ca(2+) transients is an initial trigger for mitochondrial dysfunction in skeletal muscle following denervation. Skelet. Muscle, 2017, 7(1), 6.
Federico, A.; Cardaioli, E.; Da Pozzo, P.; Formichi, P.; Gallus, G.N.; Radi, E. Mitochondria, oxidative stress and neuro-degeneration. J. Neurol. Sci., 2012, 322(1-2), 254-262.
Di Meo, S.; Iossa, S.; Venditti, P. Skeletal muscle insulin resistance: Role of mitochondria and other ROS sources. J. Endocrinol., 2017, 233(1), R15-R42.
Guillot, M.; Charles, A.L.; Chamaraux-Tran, T.N.; Bouitbir, J.; Meyer, A.; Zoll, J.; Schneider, F.; Geny, B. Oxidative stress precedes skeletal muscle mitochondrial dysfunction during experimental aortic cross-clamping but is not associated with early lung, heart, brain, liver, or kidney mitochondrial impairment.J.Vasc. Surg., 2014. 60(4), 1043-1051 e5
Tews, D.S.; Goebel, H.H. DNA fragmentation and BCL-2 expression in infantile spinal muscular atrophy. Neuromuscul. Disord., 1996, 6(4), 265-273.
Tews, D.S. Muscle-fiber apoptosis in neuromuscular diseases. Muscle Nerve, 2005, 32(4), 443-458.
Sandri, M.; El Meslemani, A.H.; Sandri, C.; Schjerling, P.; Vissing, K.; Andersen, J.L.; Rossini, K.; Carraro, U.; Angelini, C. Caspase 3 expression correlates with skeletal muscle apoptosis in Duchenne and facioscapulo human muscular dystrophy. A potential target for pharmacological treatment? J. Neuropathol. Exp. Neurol., 2001, 60(3), 302-312.
Sandri, M.; Podhorska-Okolow, M.; Geromel, V.; Rizzi, C.; Arslan, P.; Franceschi, C.; Carraro, U. Exercise induces myonuclear ubiquitination and apoptosis in dystrophin-deficient muscle of mice. J. Neuropathol. Exp. Neurol., 1997, 56(1), 45-57.
Dirks, A.J.; Leeuwenburgh, C. The role of apoptosis in age-related skeletal muscle atrophy. Sports Med., 2005, 35(6), 473-483.
Hiona, A.; Sanz, A.; Kujoth, G.C.; Pamplona, R.; Seo, A.Y.; Hofer, T.; Someya, S.; Miyakawa, T.; Nakayama, C.; Samhan-Arias, A.K.; Servais, S.; Barger, J.L.; Portero-Otin, M.; Tanokura, M.; Prolla, T.A.; Leeuwenburgh, C. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One, 2010, 5(7), e11468.
Jangamreddy, J.R.; Los, M.J. Mitoptosis, a novel mitochondrial death mechanism leading predominantly to activation of autophagy. Hepat. Mon., 2012, 12(8), e6159.
Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell, 2008, 132(1), 27-42.
Zhao, J.; Brault, J.J.; Schild, A.; Cao, P.; Sandri, M.; Schiaffino, S.; Lecker, S.H.; Goldberg, A.L. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab., 2007, 6(6), 472-483.
Dobrowolny, G.; Aucello, M.; Rizzuto, E.; Beccafico, S.; Mammucari, C.; Boncompagni, S.; Belia, S.; Wannenes, F.; Nicoletti, C.; Del Prete, Z.; Rosenthal, N.; Molinaro, M.; Protasi, F.; Fano, G.; Sandri, M.; Musaro, A. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab., 2008, 8(5), 425-436.
Mammucari, C.; Milan, G.; Romanello, V.; Masiero, E.; Rudolf, R.; Del Piccolo, P.; Burden, S.J.; Di Lisi, R.; Sandri, C.; Zhao, J.; Goldberg, A.L.; Schiaffino, S.; Sandri, M. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab., 2007, 6(6), 458-471.
Twig, G.; Shirihai, O.S. The interplay between mitochondrial dynamics and mitophagy. Antioxid. Redox Signal., 2011, 14(10), 1939-1951.
Dagda, R.K.; Cherra, S.J., III; Kulich, S.M.; Tandon, A.; Park, D.; Chu, C.T. Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission. J. Biol. Chem., 2009, 284(20), 13843-13855.
O’Leary, M.F.; Vainshtein, A.; Iqbal, S.; Ostojic, O.; Hood, D.A. Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle. Am. J. Physiol. Cell Physiol., 2013, 304(5), C422-C430.
O’Leary, M.F.; Vainshtein, A.; Carter, H.N.; Zhang, Y.; Hood, D.A. Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals. Am. J. Physiol. Cell Physiol., 2012, 303(4), C447-C454.
Narendra, D.P.; Youle, R.J. Targeting mitochondrial dysfunction: Role for PINK1 and Parkin in mitochondrial quality control. Antioxid. Redox Signal., 2011, 14(10), 1929-1938.
Youle, R.J.; Narendra, D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol., 2011, 12(1), 9-14.
Vainshtein, A.; Desjardins, E.M.; Armani, A.; Sandri, M.; Hood, D.A. PGC-1alpha modulates denervation-induced mitophagy in skeletal muscle. Skelet. Muscle, 2015, 5, 9.
Vainshtein, A.; Tryon, L.D.; Pauly, M.; Hood, D.A. Role of PGC-1alpha during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am. J. Physiol. Cell Physiol., 2015, 308(9), C710-C719.
Sarraf, S.A.; Raman, M.; Guarani-Pereira, V.; Sowa, M.E.; Huttlin, E.L.; Gygi, S.P.; Harper, J.W. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature, 2013, 496(7445), 372-376.
Ziviani, E.; Tao, R.N.; Whitworth, A.J. Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin. Proc. Natl. Acad. Sci. USA, 2010, 107(11), 5018-5023.
Mofarrahi, M.; Sigala, I.; Guo, Y.; Godin, R.; Davis, E.C.; Petrof, B.; Sandri, M.; Burelle, Y.; Hussain, S.N. Autophagy and skeletal muscles in sepsis. PLoS One, 2012, 7(10), e47265.
Romanello, V.; Sandri, M. Mitochondrial biogenesis and fragmentation as regulators of muscle protein degradation. Curr. Hypertens. Rep., 2010, 12(6), 433-439.
Grumati, P.; Coletto, L.; Sabatelli, P.; Cescon, M.; Angelin, A.; Bertaggia, E.; Blaauw, B.; Urciuolo, A.; Tiepolo, T.; Merlini, L.; Maraldi, N.M.; Bernardi, P.; Sandri, M.; Bonaldo, P. Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat. Med., 2010, 16(11), 1313-1320.
Masiero, E.; Agatea, L.; Mammucari, C.; Blaauw, B.; Loro, E.; Komatsu, M.; Metzger, D.; Reggiani, C.; Schiaffino, S.; Sandri, M. Autophagy is required to maintain muscle mass. Cell Metab., 2009, 10(6), 507-515.
Tanaka, A.; Cleland, M.M.; Xu, S.; Narendra, D.P.; Suen, D.F.; Karbowski, M.; Youle, R.J. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J. Cell Biol., 2010, 191(7), 1367-1380.
Hancock, C.R.; Han, D.H.; Chen, M.; Terada, S.; Yasuda, T.; Wright, D.C.; Holloszy, J.O. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc. Natl. Acad. Sci. USA, 2008, 105(22), 7815-7820.
Remels, A.H.; Gosker, H.R.; Schrauwen, P.; Langen, R.C.; Schols, A.M. Peroxisome proliferator-activated receptors: A therapeutic target in COPD? Eur. Respir. J., 2008, 31(3), 502-508.
Schrauwen, P.; Mensink, M.; Schaart, G.; Moonen-Kornips, E.; Sels, J.P.; Blaak, E.E.; Russell, A.P.; Hesselink, M.K. Reduced skeletal muscle uncoupling protein-3 content in prediabetic subjects and type 2 diabetic patients: Restoration by rosiglitazone treatment. J. Clin. Endocrinol. Metab., 2006, 91(4), 1520-1525.
Hornikx, M.; Van Remoortel, H.; Lehouck, A.; Mathieu, C.; Maes, K.; Gayan-Ramirez, G.; Decramer, M.; Troosters, T.; Janssens, W. Vitamin D supplementation during rehabilitation in COPD: A secondary analysis of a randomized trial. Respir. Res., 2012, 13, 84.
Sandri, M.; Lin, J.; Handschin, C.; Yang, W.; Arany, Z.P.; Lecker, S.H.; Goldberg, A.L.; Spiegelman, B.M. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc. Natl. Acad. Sci. USA, 2006, 103(44), 16260-16265.
Geng, T.; Li, P.; Yin, X.; Yan, Z. PGC-1alpha promotes nitric oxide antioxidant defenses and inhibits FOXO signaling against cardiac cachexia in mice. Am. J. Pathol., 2011, 178(4), 1738-1748.
Wenz, T. PGC-1alpha activation as a therapeutic approach in mitochondrial disease. IUBMB Life, 2009, 61(11), 1051-1062.
Brault, J.J.; Jespersen, J.G.; Goldberg, A.L. Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy. J. Biol. Chem., 2010, 285(25), 19460-19471.
Thomas, D.A.; Stauffer, C.; Zhao, K.; Yang, H.; Sharma, V.K.; Szeto, H.H.; Suthanthiran, M. Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function. J. Am. Soc. Nephrol., 2007, 18(1), 213-222.
Wu, J.; Zhang, M.; Hao, S.; Jia, M.; Ji, M.; Qiu, L.; Sun, X.; Yang, J.; Li, K. Mitochondria-targeted peptide reverses mitochondrial dysfunction and cognitive deficits in sepsis-associated encephalopathy. Mol. Neurobiol., 2015, 52(1), 783-791.
Hou, Y.; Li, S.; Wu, M.; Wei, J.; Ren, Y.; Du, C.; Wu, H.; Han, C.; Duan, H.; Shi, Y. Mitochondria-targeted peptide SS-31 attenuates renal injury via an antioxidant effect in diabetic nephropathy. Am. J. Physiol. Renal Physiol., 2016, 310(6), F547-F559.
Favero, G.; Bonomini, F.; Franco, C.; Rezzani, R. Mitochondrial dysfunction in skeletal muscle of a fibromyalgia model: The potential benefits of melatonin. Int. J. Mol. Sci., 2019, 20(3), E765.
Reiter, R.J.; Tan, D.X.; Manchester, L.C.; El-Sawi, M.R. Melatonin reduces oxidant damage and promotes mitochondrial respiration: implications for aging. Ann. N. Y. Acad. Sci., 2002, 959, 238-250.
Wang, X.; Sirianni, A.; Pei, Z.; Cormier, K.; Smith, K.; Jiang, J.; Zhou, S.; Wang, H.; Zhao, R.; Yano, H.; Kim, J.E.; Li, W.; Kristal, B.S.; Ferrante, R.J.; Friedlander, R.M. The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity. J. Neurosci., 2011, 31(41), 14496-14507.
Wang, X.; Zhu, S.; Pei, Z.; Drozda, M.; Stavrovskaya, I.G.; Del Signore, S.J.; Cormier, K.; Shimony, E.M.; Wang, H.; Ferrante, R.J.; Kristal, B.S.; Friedlander, R.M. Inhibitors of cytochrome c release with therapeutic potential for Huntington’s disease. J. Neurosci., 2008, 28(38), 9473-9485.
Zhang, Y.; Cook, A.; Kim, J.; Baranov, S.V.; Jiang, J.; Smith, K.; Cormier, K.; Bennett, E.; Browser, R.P.; Day, A.L.; Carlisle, D.L.; Ferrante, R.J.; Wang, X.; Friedlander, R.M. Melatonin inhibits the caspase-1/cytochrome c/caspase-3 cell death pathway, inhibits MT1 receptor loss and delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol. Dis., 2013, 55, 26-35.
Scarpulla, R.C.; Vega, R.B.; Kelly, D.P. Transcriptional integration of mitochondrial biogenesis. Trends Endocrinol. Metab., 2012, 23(9), 459-466.
Canto, C.; Auwerx, J. PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr. Opin. Lipidol., 2009, 20(2), 98-105.
Kanabus, M.; Heales, S.J.; Rahman, S. Development of pharmacological strategies for mitochondrial disorders. Br. J. Pharmacol., 2014, 171(8), 1798-1817.
Liu, J.; Peng, Y.; Wang, X.; Fan, Y.; Qin, C.; Shi, L.; Tang, Y.; Cao, K.; Li, H.; Long, J.; Liu, J. Mitochondrial dysfunction launches dexamethasone-induced skeletal muscle atrophy via AMPK/FOXO3 signaling. Mol. Pharm., 2016, 13(1), 73-84.
Asami, Y.; Aizawa, M.; Kinoshita, M.; Ishikawa, J.; Sakuma, K. Resveratrol attenuates denervation-induced muscle atrophy due to the blockade of atrogin-1 and p62 accumulation. Int. J. Med. Sci., 2018, 15(6), 628-637.
Gammage, P.A.; Minczuk, M. Enhanced manipulation of human mitochondrial DNA heteroplasmy in vitro using tunable mtZFN technology. Methods Mol. Biol., 2018, 1867, 43-56.
Gammage, P.A.; Van Haute, L.; Minczuk, M. Engineered mtZFNs for manipulation of human mitochondrial DNA heteroplasmy. Methods Mol. Biol., 2016, 1351, 145-162.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy