Roles of transcriptional corepressor RIP140 and coactivator PGC-1α in energy state of chronically infarcted rat hearts and mitochondrial function of cardiomyocytes

Transcriptional coactivator PPAR gamma coactivator-1 alpha (PGC-1 alpha) and corepressor receptor-interacting protein 140 (RIP140) are opposing-functional regulators in maintaining energy balance of most metabolic tissues and cells. However, the relative contributions of both factors to energy metabolism in cardiomyocytes remain largely unknown. Herein, we reported that the relative protein levels of RIP140/PGC-1 alpha were up-regulated in the failing hearts after chronic myocardial infarction (MI), and correlated negatively with the energy state index phosphocreatine (PCr)/ATP ratios. Real-time PCR analysis revealed that mRNA expressions of estrogen related receptor alpha (ERR alpha), peroxisome proliferate activated receptor alpha and beta (PPAR alpha, PPAR beta), nuclear respiratory factor 1 (NRF1) and their target genes were repressed by RIP140 and induced by PGC-1 alpha in a dose dependent manner in neonatal rat cardiomyocytes. We also observed that overexpression of RIP140 through adenovirus delivery can abrogate the PGC-1 alpha-mediated induction of mitochondrial membrane potential elevation and mitochondrial biogenesis, and activate both autophagy and apoptosis pathways. We conclude that RIP140 and PGC-1 alpha exert antagonistic role in regulating cardiac energy state and mitochondrial biogenesis. (C) 2012 Elsevier Ireland Ltd. All rights reserved.