Transcriptional coactivator PGC-1α promotes peroxisomal remodeling and biogenesis

Mitochondria and peroxisomes execute some analogous, nonredundant functions including fatty acid oxidation and detoxification of reactive oxygen species, and, in response to select metabolic cues, undergo rapid remodeling and division. Although these organelles share some components of their division machinery, it is not known whether a common regulator coordinates their remodeling and biogenesis. Here we show that in response to thermogenic stimuli, peroxisomes in brown fat tissue (BAT) undergo selective remodeling and expand in number and demonstrate that ectopic expression of the transcriptional coactivator PGC-1 alpha recapitulates these effects on the peroxisomal compartment, both in vitro and in vivo. Conversely, beta-adrenergic stimulation of PGC-1 alpha(-/-) cells results in blunted induction of peroxisomal gene expression. Surprisingly, PPAR alpha was not required for the induction of critical biogenesis factors, suggesting that PGC-1 alpha orchestrates peroxisomal remodeling through a PPAR alpha-independent mechanism. Our data suggest that PGC-1 alpha is critical to peroxisomal physiology, establishing a role for this factor as a fundamental orchestrator of cellular adaptation to energy demands.