Abstract
We investigated the expression of the nuclear-encoded genes controlling the mitochondrial properties in the mouse gastrocnemius muscle to gain insight into the mitochondrial biogenesis that occurs during the muscle degeneration/regeneration induced by freezing. In addition, we tested whether the muscle regeneration is affected by pharmacologically blocking the mitochondrial protein synthesis to elucidate the possible involvement of mitochondrial biogenesis in muscle regeneration. The activity of citrate synthase dramatically increased soon after the initial injury when the myoblasts began to differentiate into myotubes, indicating that mitochondrial biogenesis occurs early during the muscle regeneration. At the same time, the expression of mitochondrial biogenesis-related genes including PGC-1β, PRC, NRF-1, NRF-2, TFAM, mtSSB, fission 1, and Lon protease synchronized with that of the myogenic regulatory genes including MyoD and myogenin. The skeletal muscles forced to regenerate in the presence of chloramphenicol to block the mitochondrial protein synthesis were of poor repair with small myofibers and an increased amount of connective tissue. These results suggest that mitochondrial biogenesis activated early during the muscle regeneration and that mitochondrial biogenesis plays a role in muscle regeneration.
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References
Mauro A (1961) Satellite cell of skeletal muscle fibers. J Biophys Biochem Cytol 9:493–495
Hawke TJ, Garry DJ (2001) Myogenic satellite cells: physiology to molecular biology. J Appl Physiol 91:534–551
Moyes CD, Mathieu-Costello OA, Tsuchiya N, Filburn C, Hansford RG (1997) Mitochondrial biogenesis during cellular differentiation. Am J Physiol 272:C1345–C1351
Brunk CF, Yaffe D (1976) The reversible inhibition of myoblast fusion by ethidium bromide (EB). Exp Cell Res 99:310–318
Herzberg NH, Zwart R, Wolterman RA, Ruiter JP, Wanders RJ, Bolhuis PA, van den Bogert C (1993) Biochim differentiation and proliferation of respiration-deficient human myoblasts. Biochim Biophys Acta 1181:63–67
Herzberg NH, Middelkoop E, Adorf M, Dekker HL, Van Galen MJ, Van den Berg M, Bolhuis PA, Van den Bogert C (1993) Mitochondria in cultured human muscle cells depleted of mitochondrial DNA. Eur J Cell Biol 61:400–408
Korohoda W, Pietrzkowski Z, Reiss K (1993) Choramphenicol, an inhibitor of mitochondrial protein synthesis, inhibits myoblast fusion and myotube differentiation. Folia Histochem Cytobiol 31:9–13
Rochard P, Rodier A, Casas F, Cassar-Malek I, Marchal-Victorion S, Daury L, Wrutniak C, Cabello G (2000) Mitochondrial activity is involved in the regulation of myoblast differentiation through myogenin expression and activity of myogenic factors. J Biol Chem 275:2733–2744
Pawlikowska P, Gajkowska B, Hocquette JF, Orzechowski A (2006) Not only insulin stimulates mitochondriogenesis in muscle cells, but mitochondria are also essential for insulin-mediated myogenesis. Cell Prolif 39:127–145
Seyer P, Grandemange S, Busson M, Carazo A, Gamaléri F, Pessemesse L, Casas F, Cabello G, Wrutniak-Cabello C (2006) Mitochondrial activity regulates myoblast differentiation by control of c-Myc expression. J Cell Physiol 207:75–86
Hamai N, Nakamura M, Asano A (1997) Inhibition of mitochondrial protein synthesis impaired C2C12 myoblast differentiation. Cell Struct Funct 22:421–431
Duguez S, Féasson L, Denis C, Freyssenet D (2002) Mitochondrial biogenesis during skeletal muscle regeneration. Am J Physiol 282:E802–E809
Fink E, Fortin D, Serrurier B, Ventura-Clapier R, Bigard AX (2003) Recovery of contractile and metabolic phenotypes in regenerating slow muscle after notexin-induced or crush injury. J Muscle Res Cell Motil 24:421–429
Hock MB, Kralli A (2009) Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol 71:177–203
Ryan MT, Hoogenraad NJ (2007) Mitochondrial-nuclear communications. Annu Rev Biochem 76:701–722
Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88:611–638
Chen H, Chan DC (2005) Emerging functions of mammalian mitochondrial fusion and fission. Hum Mol Genet 14:R283–R289
Ventura-Clapier R, Garnier A, Veksler V (2008) Transcriptional control of mitochondrial biogenesis: the central role of PGC-1alpha. Cardiovasc Res 79:208–217
Fu GK, Markovitz DM (1998) The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner. Biochemistry 37:1905–1909
Warren GL, Hulderman T, Jensen N, McKinstry M, Mishra M, Luster MI, Simeonova PP (2002) Physiological role of tumor necrosis factor alpha in traumatic muscle injury. FASEB J 16:1630–1632
Straub V, Rafael JA, Chamberlain JS, Campbell KP (1997) Animal models for muscular dystrophy show different patterns of sarcolemmal disruption. J Cell Biol 139:375–385
Srere PA (1969) Citrate synthase. Methods Enzymol 13:3–5
van den Bosch BJ, van den Burg CM, Schoonderwoerd K, Lindsey PJ, Scholte HR, de Coo RF, van Rooij E, Rockman HA, Doevendans PA, Smeets HJ (2005) Regional absence of mitochondria causing energy depletion in the myocardium of muscle LIM protein knockout mice. Cardiovasc Res 65:411–418
Wiwi CA, Gupte M, Waxman DJ (2004) Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4alpha-deficient mice. Mol Endocrinol 18:1975–1987
Kraft CS, LeMoine CM, Lyons CN, Michaud D, Mueller CR, Moyes CD (2006) Control of mitochondrial biogenesis during myogenesis. Am J Physiol 290:C1119–C1127
Masuyama M, Iida R, Takatsuka H, Yasuda T, Matsuki T (2005) Quantitative change in mitochondrial DNA content in various mouse tissues during aging. Biochim Biophys Acta 1723:302–308
Suliman HB, Carraway MS, Welty-Wolf KE, Whorton AR, Piantadosi CA (2003) Lipopolysaccharide stimulates mitochondrial biogenesis via activation of nuclear respiratory factor-1. J Biol Chem 278:41510–41518
Schreiber SN, Knutti D, Brogli K, Uhlmann T, Kralli A (2003) The transcriptional coactivator PGC-1 regulates the expression and activity of the orphan nuclear receptor estrogen-related receptor alpha (ERRalpha). J Biol Chem 278:9013–9018
Brown JMC, Henriksson J, Salmons S (1989) Restoration of fast muscle characteristics following cessation of chronic stimulation: physiological, histochemical and metabolic changes during slow-to-fast transformation. Proc R Soc Lond B Biol Sci 235:321–346
Lamb RJ, Clark-Walker CD, Linnane AW (1968) The biogenesis of mitochondria. 4. The differentiation of mitochondrial and cytoplasmic protein synthesizing systems in vitro by antibiotics. Biochim Biophys Acta 161:415–428
Chargé SB, Rudnicki MA (2004) Cellular and molecular regulation of muscle regeneration. Physiol Rev 84:209–238
Wagatsuma A, Tamaki H, Ogita F (2006) Sequential expression of vascular endothelial growth factor, Flt-1, and KDR/Flk-1 in regenerating mouse skeletal muscle. Physiol Res 55:633–640
Wagatsuma A (2007) Endogenous expression of angiogenesis-related factors in response to muscle injury. Mol Cell Biochem 298:151–159
Tomáska L, Nosek J, Kucejová B (2001) Mitochondrial single-stranded DNA-binding proteins: in search for new functions. Biol Chem 382:179–186
Sladek R, Bader JA, Giguère V (1997) The orphan nuclear receptor estrogen-related receptor alpha is a transcriptional regulator of the human medium-chain acyl coenzyme A dehydrogenase gene. Mol Cell Biol 17:5400–5409
Vega RB, Huss JM, Kelly DP (2000) The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes. Mol Cell Biol 20:1868–1876
Remels AH, Langen RC, Schrauwen P, Schaart G, Schols AM, Gosker HR (2010) Regulation of mitochondrial biogenesis during myogenesis. Mol Cell Endocrinol 315:113–120
Andersson U, Scarpulla RC (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol 21:3738–3749
Gleyzer N, Vercauteren K, Scarpulla RC (2005) Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol 25:1354–1366
Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576:1–14
Lin J, Puigserver P, Donovan J, Tarr P, Spiegelman BM (2002) Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem 277:1645–1648
Brault JJ, Jespersen JG, Goldberg AL (2010) Peroxisome proliferator-activated receptor gamma coactivator 1alpha or 1beta overexpression inhibits muscle protein degradation, induction of ubiquitin ligases, and disuse atrophy. J Biol Chem 285:19460–19471
Szustakowski JD, Lee JH, Marrese CA, Kosinski PA, Nirmala NR, Kemp DM (2006) Identification of novel pathway regulation during myogenic differentiation. Genomics 87:129–138
Pich S, Bach D, Briones P, Liesa M, Camps M, Testar X, Palacín M, Zorzano A (2005) The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet 14:1405–1415
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 (2010) Mitochondrial fission and remodelling contributes to muscle atrophy. EMBO J 29:1774–1785
Lee S, Kim S, Sun X, Lee JH, Cho H (2007) Cell cycle-dependent mitochondrial biogenesis and dynamics in mammalian cells. Biochem Biophys Res Commun 357:111–117
Hyde BB, Twig G, Shirihai OS (2010) Organellar vs cellular control of mitochondrial dynamics. Semin Cell Dev Biol. doi:10.1016/j.semcdb.2010.01.003
Bota DA, Ngo JK, Davies KJ (2005) Downregulation of the human Lon protease impairs mitochondrial structure and function and causes cell death. Free Radic Biol Med 38:665–677
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This study was supported in part by Grant-in Aid for Scientific Research (C) from the Japan Society for the promotion of Science (Grant No. 22500658 to A.W.).
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Wagatsuma, A., Kotake, N. & Yamada, S. Muscle regeneration occurs to coincide with mitochondrial biogenesis. Mol Cell Biochem 349, 139–147 (2011). https://doi.org/10.1007/s11010-010-0668-2
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DOI: https://doi.org/10.1007/s11010-010-0668-2