Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscl
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ORIGINAL PAPER
Expression of nuclear-encoded genes involved in mitochondrial biogenesis and dynamics in experimentally denervated muscle Akira Wagatsuma & Naoki Kotake & Kunihiko Mabuchi & Shigeru Yamada
Received: 29 November 2010 / Accepted: 22 February 2011 / Published online: 11 March 2011 # University of Navarra 2011
Abstract The abundance, morphology, and functional properties of mitochondria become altered in response to denervation. To gain insight into the regulation of this process, mitochondrial enzyme activities and gene expression involved in mitochondrial biogenesis and dynamics in mouse gastrocnemius muscle was investigated. Sciatic nerve transactions were performed on mice, and then gastrocnemius muscles were isolated at days 5 and 30 after surgery. Muscle weight was decreased significantly by 15% and 62% at days 5 and 30 after surgery, respectively. The activity of citrate synthase, a marker of oxidative enzyme, was reduced significantly by 31% and 53% at days 5 and 30, respectively. Enzyme histochemical analysis revealed that subsarcolemmal mitochondria were largely lost than intermyofibrillar mitochondria at day 5, and this trend was further progressed at A. Wagatsuma : S. Yamada Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan A. Wagatsuma (*) : K. Mabuchi Graduate School of Information Science and Technology, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, Japan e-mail: [email protected] N. Kotake Department of Advanced Interdisciplinary Studies (AIS), Graduate School of Engineering, The University of Tokyo, Tokyo, Japan
day 30 after surgery. Expression levels of peroxisome proliferator-activated receptor, γ coactivator 1 (PGC1)α, estrogen-related receptor α (ERRα), and mitofusin 2 were down-regulated throughout the experimental period, whereas those of PGC-1β, PRC, nuclear respiratory factor (NRF)-1, NRF-2, TFAM, and Lon protease were down-regulated at day 30 after surgery. These results suggest that PGC-1α, ERRα, and mitofusin 2 may be important factors in the process of denervation-induced mitochondrial adaptation. In addition, other PGC-1 family of transcriptional coactivators and DNA binding transcription factors may also contribute to mitochondrial adaptation after early response to denervation. Keywords Denervation . Mitochondrial adaptation . PGC-1 . ERRα . Mitofusin 2
Introduction The abundance, morphology, and functional properties of mitochondria are dynamically regulated in response to alterations in neuromuscular activity. Basically, increased neuromuscular activity (e.g., exercise, endurance training, and electrical stimulation) promotes mitochondrial biogenesis [23], whereas reduced neuromuscular activity (e.g., denervation, immobilization, spaceflight, spinal cord isolation, and hindlimb unloading) demotes mitochondrial biogenesis [5, 48, 57]. Mitochondrial biogenesis requires the synthesis, im-
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port, and incorporation of proteins and lipids to the existing mitochondrial reticulum, as well as replication of the mitochondria DN
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