A truncated PPAR gamma 2 localizes to mitochondria and regulates mitochondrial respiration in brown adipocytes

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a key regulator of brown adipocyte differentiation and thermogenesis. The PPAR gamma gene produces two isoforms, PPAR gamma 1 and PPAR gamma 2. PPAR gamma 2 is identical to PPAR gamma 1 except for additional 30 amino acids present in the N-terminus of PPAR gamma 2. Here we report that the C-terminally truncated form of PPAR gamma 2 is predominantly present in the mitochondrial matrix of brown adipocytes and that it binds to the D-loop region of mitochondrial DNA (mtDNA), which contains the promoter for mitochondrial electron transport chain (ETC) genes. Expression of mitochondrially targeted MLS-PPAR gamma 2 in brown adipocytes increases mtDNA-encoded ETC gene expression concomitant with enhanced mitochondrial respiration. These results suggest that direct regulation of mitochondrially encoded ETC gene expression by mitochondrial PPAR gamma 2, in part, underlies the isoform-specific role for PPAR gamma 2 in brown adipocytes.