title: Deletion of heart-type cytochrome c oxidase subunit 7a1 impairs skeletal muscle angiogenesis and oxidative phosphorylation.
abstract: Oxidative metabolism is needed for sustained skeletal muscle function. A key component of such metabolism is cytochrome c oxidase, the 13-subunit terminal complex of the mitochondrial electron transport chain. We used mice null for one of the two isoforms of Cox subunit 7a, heart/skeletal muscle-specific Cox7a1, to examine the cellular and functional responses of muscle adaptation in response to mitochondrial dysfunction. Specifically we determined if deletion of Cox7a1 would (1) limit exercise capacity, and (2) alter genes responsible for skeletal muscle capillarity and mitochondrial biogenesis. Sixteen male mice (Cox7a1 null mice, n = 8, and littermate controls, n = 8) performed incremental and run-to-exhaustion treadmill tests. The hindlimb muscles for both groups were analysed. The results indicated that capillary indices were reduced (by 30.7–44.9%) in the Cox7a1 null mice relative to controls. In addition, resting ATP levels and Cox specific activity were significantly reduced (>60%) in both glycolytic and oxidative muscle fibre types despite an increase in a major regulator of mitochondrial biogenesis, PGC-1β. These changes in the skeletal muscle resulted in exercise intolerance for the Cox7a1 null mice. Thus, our data indicate that deletion of the Cox7a1 isoform results in reduced muscle bioenergetics and hindlimb capillarity, helping to explain the observed impairment of muscle structure and function.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University, Eugene Applebaum College of Pharmacy & Health Sciences, Detroit, MI 48201, USA.
authors.forename: Icksoo
authors.initials: I
authors.lastname: Lee
authors.forename: Maik
authors.initials: M
authors.lastname: Hüttemann
authors.forename: Jenney
authors.initials: J
authors.lastname: Liu
authors.forename: Lawrence I
authors.initials: LI
authors.lastname: Grossman
authors.forename: Moh H
authors.initials: MH
authors.lastname: Malek
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000502:physiology*; D017079:Exercise Tolerance; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology; D018919:Neovascularization, Physiologic; D010085:Oxidative Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*
chemical_list: D003576:Electron Transport Complex IV; C573492:cytochrome c oxidase subunit 7a1, mouse