The role of mitochondrial membrane phospholipids in muscle mass homeostasis during overloading

Abstract

Skeletal muscle is a structurally intricate and heterogenous tissue made up of individual fibers that differ in size, metabolic and contractile properties, and differs within and between organisms. Skeletal muscle is also very dynamic and can adapt to external stimuli supported by a number of cell signalling pathways. For example, muscle cells can increase in size via a process known as hypertrophy which has been studied using different models such as tenotomy. It has been shown in a rodent model of compensatory plantaris muscle hypertrophy induced by soleus and gastrocnemius tenotomy that cardiolipin (CL, mitochondrial membrane phospholipid) content and composition and tafazzin (Taz, CL remodelling enzyme) protein expression increases. However, it is still not known if protein content changes to Taz, or enzymes responsible for CL biosynthesis, precede or follow changes to CL content and composition during this adaptive response. As such, this study examined the temporal relationship (days 3, 7, 10, and 14) between the protein content of CL biosynthetic and remodelling enzymes and CL content on the adaptive response of skeletal muscle to mechanical overload via tenotomy. There was a decrease in CL despite no change in Taz protein content. Of the CL biosynthetic enzymes examined, PGS1 and CRLS1 showed significant increases in protein content post tenotomy. The greatest fold changes in TAMM41 and CRLS1 occurred simultaneously to that of CL, while PTPMT1’s changes occurred both simultaneously and after changes in CL content. PGS1 did not show any fold changes. Finally, the content of PE and PC (substrates of Taz for CL remodeling), both did not change. Thus, it can be inferred that 14 days post tenotomy in overloaded plantaris, de novo CL biosynthesis is not required but instead may rely on currently available CL for remodelling with no required change to Taz content.