Time‐dependent changes in autophagy, mitophagy and lysosomes in skeletal muscle during denervation‐induced disuse

Abstract

He then pursued an MSc under the supervision of Dr Michael Connor. Matthew subsequently worked towards his PhD as a member of the Muscle Health Research Centre at York University under the supervision of Dr David Hood. His work focused on skeletal muscle autophagy, mitophagy and lysosome biogenesis with disuse, ageing and exercise. Matthew is currently a postdoctoral fellow at the University of Ottawa, investigating mechanisms by which mitochondria regulate muscle stem cell homeostasis and function.

Is denervation‐induced transcription factor EB translocation hitting an mTOR nerve?

“…The acute activation of mTORC1 may explain the absence of atrophy and general maintenance of oxidative capacity at 1 day in the study by Triolo et al. (2022). However, persistent mTORC1 activation by denervation does not seem to prevent the increase in autophagy proteins Atg7 and Beclin1 at 3 and 7 days, likely due to a negative feedback loop.…”

“…In a study by Masiero et al (2009), the inhibition of autophagy during denervation using Atg7 null mice accelerated rates of muscle loss due to upregulation of the ubiquitin-proteasome system. Perhaps the acute (1 and 3 days) upregulation of autophagy and mitophagy flux seen by Triolo et al (2022) is an attempt to maintain muscle quality by removing dysfunctional proteins/mitochondria. Autophagy might then become exhausted and is reduced below levels seen in control mice, resulting in the more rapid atrophy seen in the final 4 days compared to the initial 3 days of denervation.…”

“…Despite these novel findings by Triolo et al (2022) in rodents, the application and translation of these findings should be taken in stride when making inferences to humans, due to the inherent species-specific differences between these two physiological models. For instance, it has been reported that rodents have faster mRNA turnover, protein turnover and metabolic rate (2.5×, 9.6× and 6.4×, respectively) relative to humans (Agoston, 2017).…”

“…space flight or >50 days of bed rest, such as that seen in comas). As such, the objectives from Triolo et al (2022) should be replicated in humans to establish whether more relevant forms of inactivity or disuse (i.e. step-reduction or immobilization) result in similar or less pronounced time-dependent changes in mitophagy and lysosomal flux.…”

“…Recently in The Journal of Physiology , Triolo et al. (2022) aimed to investigate the time‐dependent changes in autophagy and mitophagy flux in response to denervation (Triolo et al., 2022). Importantly, they also sought to examine the often‐underappreciated role of the lysosome in these processes.…”