Expression of mitochondrial fission and fusion regulatory proteins in skeletal muscle during chronic use and disuse

Introduction: The mitochondrial network within cells is mediated by fission and fusion processes. Methods: We investigated the expression of the proteins responsible for these events during conditions of altered oxidative capacity. Results: With chronic contractile activity, the mitochondrial reticulum increased in size, along with concomitant increases in the fusion proteins Opa1 and Mfn2 (by 36% and 53%; P < 0.05). When we induced muscle disuse through denervation for 7 days, fragmented mitochondria were observed, along with significant decreases in the expression of Mfn2 and Opa1 (by 84% and 70%). To assess the effects of aging on mitochondrial morphology, young (5 month) and aged (35 month) Fisher 344 Brown Norway rats were used. Aged animals also possessed smaller mitochondria and displayed increased levels of fission proteins. Conclusions: Chronic muscle use increases the ratio of fusion:fission proteins, leading to reticular mitochondria, whereas muscle disuse and aging result in a decrease in this ratio, culminating in fragmented organelles. Muscle Nerve 48: 963–970, 2013

[1]  D. Turnbull,et al.  Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study. , 2013, Journal of applied physiology.

[2]  K. Davies,et al.  Integrative and Translational Physiology : Integrative Aspects of Energy Homeostasis and Metabolic Diseases Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training , 2012 .

[3]  K. Mabuchi,et al.  Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle , 2011, Journal of Physiology and Biochemistry.

[4]  A. Wagatsuma,et al.  Mitochondrial adaptations in skeletal muscle to hindlimb unloading , 2011, Molecular and Cellular Biochemistry.

[5]  C. Zechner,et al.  Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity. , 2010, Cell metabolism.

[6]  M. Sandri,et al.  Mitochondrial Biogenesis and Fragmentation as Regulators of Muscle Protein Degradation , 2010, Current hypertension reports.

[7]  L. Ji,et al.  Response of mitochondrial fusion and fission protein gene expression to exercise in rat skeletal muscle. , 2010, Biochimica et biophysica acta.

[8]  H. Pilegaard,et al.  The role of PGC-1alpha on mitochondrial function and apoptotic susceptibility in muscle. , 2009, American journal of physiology. Cell physiology.

[9]  Xiongwei Zhu,et al.  Amyloid-β overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins , 2008, Proceedings of the National Academy of Sciences.

[10]  Keir J. Menzies,et al.  Mitochondrial function and apoptotic susceptibility in aging skeletal muscle , 2008, Aging cell.

[11]  D. Hood,et al.  Effect of chronic contractile activity on SS and IMF mitochondrial apoptotic susceptibility in skeletal muscle. , 2007, American journal of physiology. Endocrinology and metabolism.

[12]  Michael F. N. O'Leary,et al.  Effect of denervation on mitochondrially mediated apoptosis in skeletal muscle. , 2007, Journal of applied physiology.

[13]  Rachel M. Devay,et al.  Mitochondrial Inner-Membrane Fusion and Crista Maintenance Requires the Dynamin-Related GTPase Mgm1 , 2006, Cell.

[14]  B. Spiegelman,et al.  Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism. , 2006, Endocrine reviews.

[15]  Marco Castagneto,et al.  Expression of Mfn2, the Charcot-Marie-Tooth neuropathy type 2A gene, in human skeletal muscle: effects of type 2 diabetes, obesity, weight loss, and the regulatory role of tumor necrosis factor alpha and interleukin-6. , 2005, Diabetes.

[16]  A. Russell,et al.  Mitofusins 1/2 and ERRα expression are increased in human skeletal muscle after physical exercise , 2005, The Journal of physiology.

[17]  D. Chan,et al.  Disruption of Fusion Results in Mitochondrial Heterogeneity and Dysfunction* , 2005, Journal of Biological Chemistry.

[18]  M. Sheetz,et al.  Mitochondrial Function and Actin Regulate Dynamin-Related Protein 1-Dependent Mitochondrial Fission , 2005, Current Biology.

[19]  R. Jagasia,et al.  DRP-1-mediated mitochondrial fragmentation during EGL-1-induced cell death in C. elegans , 2005, Nature.

[20]  A. Garnier,et al.  The FASEB Journal • Research Communication Coordinated , 2022 .

[21]  Y. Tsujimoto,et al.  Fzo1, a Protein Involved in Mitochondrial Fusion, Inhibits Apoptosis* , 2004, Journal of Biological Chemistry.

[22]  J. Pevsner,et al.  Mitochondrial fission proteins regulate programmed cell death in yeast. , 2004, Genes & development.

[23]  R. Youle,et al.  Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. , 2004, Molecular biology of the cell.

[24]  Yuichi Yamasaki,et al.  Scanning electron-microscopic studies on the three-dimensional structure of mitochondria in the mammalian red, white and intermediate muscle fibers , 2004, Cell and Tissue Research.

[25]  J. Martinou,et al.  hFis1, a Novel Component of the Mammalian Mitochondrial Fission Machinery* , 2003, Journal of Biological Chemistry.

[26]  D. Hood,et al.  PPARγ coactivator-1α expression during thyroid hormone-and contractile activity-induced mitochondrial adaptations , 2003 .

[27]  J. Zierath,et al.  Mitofusin-2 Determines Mitochondrial Network Architecture and Mitochondrial Metabolism , 2003, The Journal of Biological Chemistry.

[28]  G. Attardi,et al.  MtDNA mutations in aging and apoptosis. , 2003, Biochemical and biophysical research communications.

[29]  Erik E. Griffin,et al.  Mitofusins Mfn1 and Mfn2 coordinately regulate mitochondrial fusion and are essential for embryonic development , 2003, The Journal of cell biology.

[30]  D. Hood,et al.  PPARgamma coactivator-1alpha expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. , 2003, American journal of physiology. Cell physiology.

[31]  Jing He,et al.  Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. , 2002, Diabetes.

[32]  S. Frank,et al.  The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. , 2001, Developmental cell.

[33]  R. Bronson,et al.  Pathologic Characterization of Brown Norway, Brown Norway × Fischer 344, and Fischer 344 × Brown Norway Rats With Relation to Age , 1996, The journals of gerontology. Series A, Biological sciences and medical sciences.

[34]  D. Hood,et al.  Chronic stimulation-induced changes in mitochondria and performance in rat skeletal muscle. , 1993, Journal of applied physiology.

[35]  D. Hood,et al.  Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions. , 1993, The American journal of physiology.

[36]  D. Hood,et al.  Mitochondrial adaptations in denervated muscle: relationship to muscle performance. , 1991, The American journal of physiology.

[37]  H. Hoppeler,et al.  The similarity of mitochondrial distribution in equine skeletal muscles of differing oxidative capacity. , 1988, The Journal of experimental biology.

[38]  G. Brooks,et al.  Effects of endurance training on a mitochondrial reticulum in limb skeletal muscle. , 1987, Archives of biochemistry and biophysics.

[39]  E. Weibel,et al.  Mitochondrial distribution in relation to changes in muscle metabolism in rat soleus. , 1986, Respiration physiology.

[40]  V. Skulachev,et al.  Ontogenesis of mitochondrial reticulum in rat diaphragm muscle. , 1981, European journal of cell biology.

[41]  K. Rethoret,et al.  Temporal analysis of the nuclear cycle by serial section electron microscopy of the fungus, Saprolegnia ferax. , 1980, European journal of cell biology.

[42]  L. Larsson,et al.  Skeletal muscle metabolism and ultrastructure in relation to age in sedentary men. , 1978, Acta physiologica Scandinavica.

[43]  V. Skulachev,et al.  Mitochondrial framework (reticulum mitochondriale) in rat diaphragm muscle. , 1978, Biochimica et biophysica acta.

[44]  R. Miledi,et al.  Some mitochondrial changes in denervated muscle. , 1968, Journal of cell science.