Transcriptional coactivator PGC-1alpha 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-1α recapitulates these effects on the peroxisomal compartment, both in vitro and in vivo. Conversely, β-adrenergic stimulation of PGC-1α(-/-) cells results in blunted induction of peroxisomal gene expression. Surprisingly, PPARα was not required for the induction of critical biogenesis factors, suggesting that PGC-1α orchestrates peroxisomal remodeling through a PPARα-independent mechanism. Our data suggest that PGC-1α is critical to peroxisomal physiology, establishing a role for this factor as a fundamental orchestrator of cellular adaptation to energy demands.
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Alessia
A
Bagattin
Lynne
L
Hugendubler
Elisabetta
E
Mueller
D052437:Adipocytes, Brown / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D055786:Gene Knockout Techniques; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020675:Peroxisomes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors