The effects of chronic muscle use and disuse on cardiolipin metabolism

Mitochondrial membranes have a diverse structure composed of numerous phospholipids, including cardiolipin (CL). Several processes are required to synthesize· and remodel CL. We previously demonstrated that CL content increases with chronic muscle use, and decreases with denervation. To investigate the mechanisms underlying these effects, we measured the mRNA expression of CL metabolism enzymes, including 1) CL synthesis enzymes Cardiolipin synthase (CLS) and CTP:PA-cytidylyltransferase-1 (CDS-1 ); 2) remodelling enzymes Tafazzin (Taz) and Acyl-CoA:lysocardiolipin acyltransferase-1 (ALCAT1); and 3) outer membrane CL enzymes, Mitochondrial phospholipase D (MitoPLD) and phospholipid scramblase 3 (Plscr3). We found that the transcriptional coactivator PGC-1? regulates the mRNA levels of CDS-1 and ALCAT1, thus playing a role in both CL synthesis and remodelling. We found that all three enzyme categories were altered by our conditions, but unaffected by age, suggesting that chronic muscle use and disuse have divergent influences on the expression of mRNAs encoding enzymes involved in CL metabolism.