Mitophagy in maintaining skeletal muscle mitochondrial proteostasis and metabolic health with ageing

Abstract

Skeletal muscle is important for overall functionality and health. Ageing is associated with an accumulation of damage to mitochondrial DNA and proteins. In particular, damage to mitochondrial proteins in skeletal muscle, which is a loss of mitochondrial proteostasis, contributes to tissue dysfunction and negatively impacts systemic health. Therefore, understanding the mechanisms underlying the regulation of mitochondrial proteostasis and how those mechanisms change with age is important for the development of interventions to promote healthy ageing. Herein, we examine how impairment in the selective degradation of damaged/dysfunctional mitochondria through mitophagy may play a central role in the loss of mitochondrial proteostasis in skeletal muscle ageing, as well as its broader implications for systemic health. Further, we explore how stimulating mitophagy through exercise may promote healthy ageing.

Keywords: aging; mitochondria; mitophagy; proteostasis; skeletal muscle.

Figure 1. Proposed role for mitophagy as a main contributor to loss of mitochondrial proteostasis with age

Figure 2. Current model for autophagy/mitophagy

Proteins that have been studied in skeletal muscle are in green. Proteins that have been described to be negatively impacted in the context of ageing (i.e. expression or function) are indicated with an asterisk (^*).