title: Disconnecting mitochondrial content from respiratory chain capacity in PGC-1-deficient skeletal muscle.
abstract: The transcriptional coactivators PGC-1α and PGC-1β are widely thought to be required for mitochondrial biogenesis and fiber typing in skeletal muscle. Here, we show that mice lacking both PGC-1s in myocytes do indeed have profoundly deficient mitochondrial respiration but, surprisingly, have preserved mitochondrial content, isolated muscle contraction capacity, fiber-type composition, in-cage ambulation, and voluntary running capacity. Most of these findings are recapitulated in cell culture and, thus, are cell autonomous. Functional electron microscopy reveals normal cristae density with decreased cytochrome oxidase activity. These data lead to the following surprising conclusions: (1) PGC-1s are in fact dispensable for baseline muscle function, mitochondrial content, and fiber typing, (2) endurance fatigue at low workloads is not limited by muscle mitochondrial capacity, and (3) mitochondrial content and cristae density can be dissociated from respiratory capacity.
authors.affiliation: Cardiovascular Institute, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Rowe
authors.forename: Ian S
authors.initials: IS
authors.lastname: Patten
authors.forename: Zsuzsanna K
authors.initials: ZK
authors.lastname: Zsengeller
authors.forename: Riyad
authors.initials: R
authors.lastname: El-Khoury
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Okutsu
authors.forename: Sophia
authors.initials: S
authors.lastname: Bampoh
authors.forename: Nicole
authors.initials: N
authors.lastname: Koulisis
authors.forename: Caitlin
authors.initials: C
authors.lastname: Farrell
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hirshman
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
authors.forename: Pierre
authors.initials: P
authors.lastname: Rustin
authors.forename: Zolt
authors.initials: Z
authors.lastname: Arany
mesh_terms: D000818:Animals; D002460:Cell Line; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D003576:Electron Transport Complex IV