Role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) in regulating mitochondrial energy effciency in skeletal muscle

Abstract

Previous studies have shown that exercise training improves mitochondrial energy effciency in skeletal muscle, but the molecular mechanism is unclear. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) is a transcriptional co-activator that coordinately regulates exercise-induced mitochondrial biogenesis and quality control. This study aimed to test the hypothesis that PGC-1a is involved in the improvement of mitochondrial energy effciency in skeletal muscle by using a skeletal muscle-specific PGC-1a overexpression mouse model. Ten to twelve-week-old skeletal muscle-specific PGC-1a transgenic mice (MCK-PGC-1a) and their wildtype littermates (WT) were used. Protein levels of oxidative phosphorylation (OXPHOS) subunits in skeletal muscle were determined by Western blot analysis. The rate of O2 consumption ( JO2) and ATP production ( JATP) in isolated mitochondria from skeletal muscle were evaluated using high-resolution respirometry and fluorometry, respectively, and mitochondrial energy effciency (ATP produced per O2 consumed, or P/O) was calculated. Overexpression of PGC-1a in skeletal muscle did not affect body weights and muscle weights. Consistent with previous studies, MCK-PGC-1a mice had significantly higher OXPHOS protein content than WT mice. On the other hand, JO2, JATP, and P/O in isolated muscle mitochondria were not different between genotypes. Our results suggest that exercise training-induced improvement in muscle mitochondrial energy effciency is not mediated by PGC-1a. This research is supported by NIH grant DK107397 to K.F. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.