Perspectives on the interpretation of mitochondrial responses during skeletal muscle disuse‐induced atrophy

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Reductions in skeletal muscle mitochondrial respiration or increases in mitochondrial reactive oxygen species (ROS) are often interpreted as ‘mitochondrial dysfunctions’. However, such changes can also occur as intentional programmed responses to stressors. The term ‘mitochondrial dysfunction’ could therefore consider the net impact of such responses on other cellular functions. In the case of disuse‐induced skeletal muscle atrophy, lower mitochondrial respiration, increased ROS and increased mitochondrial‐linked apoptosis have been associated with muscle loss. Such observations support hypotheses that mitochondria contribute to atrophy. If true, there are exciting opportunities for exploring therapeutic strategies that prevent such changes in mitochondrial metabolism. These observations might also support alternative hypotheses where mitochondria are intentionally reprogrammed to serve specific purposes, such as a recalibration of ATP supply to reduced ATP demand during disuse. The goal of this review is to describe what is known regarding skeletal muscle mitochondrial functional responses to muscle disuse, as well as to discuss how these foundational discoveries might lead to new directions that determine whether mitochondrial responses to disuse are causal of atrophy or are adaptive in nature. Three critical questions for consideration include: (1) when is a change in mitochondrial function ‘dysfunctional’; (2) how might changes in mitochondrial function represent intentional reprogramming to serve specific purposes; and (3) what factors should be considered when constructing experimental designs to determine the role of mitochondrial functional responses to disuse? Understanding when mitochondrial functional remodelling are dysfunctions or adaptive responses could inform new therapeutic approaches to maintain muscle mass during periods of disuse. image

This publication has 74 references indexed in Scilit: