Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2793616 | Cell Metabolism | 2007 | 12 Pages |
SummarySkeletal muscle must perform different kinds of work, and distinct fiber types have evolved to accommodate these. Previous work had shown that the transcriptional coactivator PGC-1α drives the formation of type I and IIA muscle fibers, which are “slow-twitch” and highly oxidative. We show here that transgenic expression of PGC-1β, a coactivator functionally similar to but distinct from PGC-1α, causes a marked induction of IIX fibers, which are oxidative but have “fast-twitch” biophysical properties. PGC-1β coactivates the MEF2 family of transcription factors to stimulate the type IIX myosin heavy chain (MHC) promoter. PGC-1β transgenic muscle fibers are rich in mitochondria and are highly oxidative, at least in part due to coactivation by PGC-1β of ERRα and PPARα. Consequently, these transgenic animals can run for longer and at higher work loads than wild-type animals. Together, these data indicate that PGC-1β drives the formation of highly oxidative fibers containing type IIX MHC.