4.5 Article

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4-week hindlimb unloading

Journal

IUBMB LIFE
Volume 64, Issue 11, Pages 901-910

Publisher

WILEY
DOI: 10.1002/iub.1087

Keywords

skeletal muscle atrophy; mitochondria dynamics remodeling; unloading

Funding

  1. opening foundation of the State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center [SMFA10K07]
  2. Foundation of Xi'an Jiaotong University
  3. New Century Excellent Talents in University
  4. National Natural Science Foundation of China [31070740]

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Mitochondrial dynamics is highly involved in muscle atrophy, the slow twitch muscle as soleus, preferentially affected by hindlimb unloading (HU), was well characterized by mitochondrial dysfunction in biogenesis. However, the fast twitch muscles like tibialis anterior (TA) and gastrocnemius (GAS), which are the most massive parts of the hindlimb muscles, are less elucidated on mitochondrial adaptations responding to HU. To investigate the mitochondrial dynamic responses and the involved molecules mediating atrophy in TA and GAS, we studied a 4-week HU mouse model. We found GAS was preferentially affected to atrophy by unloading compared with TA. Furthermore, the depressed mitochondrial biogenesis occurred, accounting for mitochondrial loss in GAS by unloading. PGC-1a, as well as its transcriptional/post-translational modification regulators, such as p-CREB, SIRT1, and p-AMPK, were consistently reduced in response to unloading in GAS. Molecules relevant to autophagy, mitochondrial fusion, and fission, were compromised following unloading both in TA and GAS. These results suggested that TA exhibited resistance to unloading induced muscle atrophy while GAS presented significant mitochondrial loss, which might be due to the mitochondrial biogenesis suppressed by the inactivation of PGC-1a. However, both in TA and GAS muscles, a similar sedentary mitochondrial dynamics of mitochondrial fusion and fission was induced by unloading though TA exhibited little muscle atrophy. (c) 2012 IUBMB, IUBMB Life, 64(11): 901910, 2012

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