title: Mitochondrial adaptations in skeletal muscle to hindlimb unloading.
abstract: To gain insight into the regulation of mitochondrial adaptations to hindlimb unloading (HU), the activity of mitochondrial enzymes and the expression of nuclear-encoded genes which control mitochondrial properties in mouse gastrocnemius muscle were investigated. Biochemical and enzyme histochemical analysis showed that subsarcolemmal mitochondria were lost largely than intermyofibrillar mitochondria after HU. Gene expression analysis revealed disturbed or diminished gene expression patterns. The three main results of this analysis are as follows. First, in contrast to peroxisome proliferator-activated receptor γ coactivator 1 β (PGC-1β) and PGC-1-related coactivator, which were down-regulated by HU, PGC-1α was up-regulated concomitant with decreased expression of its DNA binding transcription factors, PPARα, and estrogen-related receptor α (ERRα). Moreover, there was no alteration in expression of nuclear respiratory factor 1, but its downstream target gene, mitochondrial transcription factor A, was down-regulated. Second, both mitofusin 2 and fission 1, which control mitochondrial morphology, were down-regulated. Third, ATP-dependent Lon protease, which participates in mitochondrial-protein degradation, was also down-regulated. These findings suggest that HU may induce uncoordinated expression of PGC-1 family coactivators and DNA binding transcription factors, resulting in reducing ability of mitochondrial biogenesis. Furthermore, down-regulation of mitochondrial morphology-related genes associated with HU may be also involved in alterations in intracellular mitochondrial distribution.
authors.affiliation: Department of Life Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan. wagatsuma1969@yahoo.co.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Wagatsuma
authors.forename: Naoki
authors.initials: N
authors.lastname: Kotake
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawachi
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiozuka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamada
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Matsuda
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002950:Citrate (si)-Synthase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D019417:Hindlimb Suspension / Q000502:physiology*; D051379:Mice; D008931:Mitochondria, Muscle / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D002950:Citrate (si)-Synthase; D009124:Muscle Proteins; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011960:Receptors, Estrogen; D044843:SKP Cullin F-Box Protein Ligases; D013385:Succinate Dehydrogenase; D015534:Trans-Activators; D014157:Transcription Factors; D000097983:ERRalpha Estrogen-Related Receptor; C485290:Ppargc1a protein, mouse; C486691:Fbxo32 protein, mouse