Transcriptional regulation of temperature-induced remodeling of muscle bioenergetics in goldfish

Bremer K, Monk CT, Gurd BJ, Moyes CD. Transcriptional regulation of temperature-induced remodeling of muscle bioenergetics in goldfish. Am J Physiol Regul Integr Comp Physiol 303: R150-R158, 2012. First published May 23, 2012; doi:10.1152/ajpregu.00603.2011.-Central to mammalian mitochondrial biogenesis is the transcriptional master regulator peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 alpha (PGC-1 alpha), and a network of DNA-binding proteins it coactivates. We explored the role of this pathway in muscle mitochondrial biogenesis in response to thermal acclimation in goldfish (Carassius auratus). We investigated the transcriptional response of PGC-1 alpha, PGC-1 beta, and their antagonist the nuclear receptor interacting protein 1 (RIP140), as well as the mRNA and protein patterns of DNA-binding proteins that bind PGC-1, including nuclear respiratory factors (NRF) 1 and 2, retinoid X receptor alpha (RXR alpha), estrogen-related receptor alpha (ERR alpha), thyroid receptor alpha-1 (TR alpha-1), PPAR alpha, and PPAR beta/delta, and the host cell factor 1 (HCF1), which links PGC-1 and NRF-2. Cold-acclimated (4 degrees C) fish had higher COX activities (4.5-fold) and COX4-1 mRNA levels (3.5-fold per total RNA; 6.5-fold per gram tissue) than warm-acclimated (32 degrees C) fish. The transcription factor patterns were profoundly influenced by changes in RNA per gram tissue (2-fold higher in cold fish) and nuclear protein content (2-fold higher in warm fish). In cold-acclimated fish, mRNA per gram tissue was elevated for PGC-1 beta, RIP140, NRF-1, HCF1, NRF-2 alpha, NRF-2 beta-2, ERR alpha, PPAR beta/delta, and RXR alpha, but other transcriptional regulators either did not change (PGC-1 alpha, PPAR alpha) or even decreased (TR alpha-1). Nuclear protein levels in cold-acclimated fish were higher only for NRF-1; other proteins were either unaffected (NRF-2 alpha, ERR alpha) or decreased (NRF-2 beta 1/2, TR alpha, RXR alpha). Collectively, these data support the role for NRF-1 in regulating cold-induced mitochondrial biogenesis in goldfish, with effects mediated by PGC-1 beta, rather than PGC-1 alpha.