Accumulation of high-energy phosphates blocks the expression of mitochondrial biogenesis markers and slow-type myosin in soleus muscle under 24 hours of rat hindlimb suspension

Abstract

Under the initial stage of muscle mechanical unloading, the skeletal muscle undergo accumulation of high-energy phosphates followed by AMP-dependent proteinkinase (AMPK) inactivation. Since AMPK is known to activate mitochondrial biogenesis, it cannot be excluded that AMPK inactivation results in oxidative potential decrease at the later stages of muscle unloading. We decided to test the role of the accumulation of high-energy phosphates in skeletal muscle fibers in the inactivation of mitochondrial biogenesis regulators at an early stage of muscle unloading. To reduce the ATP/ADP ratio, we used beta-guanidine propionic acid, and the obtained data indicating that already during the first day of simulated microgravity, the accumulation of high-energy phosphates can reduce the expression level of mRNA of the key regulator of mitochondrial biogenesis PGC-1α, the transcription factor TFAM, as well as the mitochondrial fusion regulator - mitofusin-1. A number of other parameters of mitochondrial signaling were not subject to changes at this time-point. Thus, we demonstrated the role of the ATP/ADP ratio in the inactivation of several regulators of mitochondrial biogenesis in the postural soleus muscle at an early stage of functional unloading.

Keywords: Gene expression; Hindlimb suspension; Mitochondrial biogenesis; Muscle unloading; Skeletal muscle.