title: Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4-week hindlimb unloading.
abstract: 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-1α, 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-1α. 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.
authors.affiliation: Institute of Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University School of Life Science and Technology, Xi'an 710049, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Peng
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Cui
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wu
authors.forename: Airong
authors.initials: A
authors.lastname: Qian
authors.forename: Peng
authors.initials: P
authors.lastname: Shang
authors.forename: Lina
authors.initials: L
authors.lastname: Qu
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
authors.forename: Jiangang
authors.initials: J
authors.lastname: Long
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology*; D063154:Mitochondrial Dynamics; D063269:Mitochondrial Turnover; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000503:physiopathology*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger