Sestrin regulates cellular homeostasis through modulating mitochondrial function

For years, the function of Sestrin proteins has been assigned to antioxidant protection and regulation of mTOR complexes 1 and 2. However, recent data demonstrate that Sestrins have a new role in the regulation of mitochondrial functions through incompletely understood mechanisms. These include Sestrin involvement in the control of mitochondrial biogenesis, respiration and mitophagy. Machado et al. describe a key role of Sestrin2 in the regulation of mitochondrial function in myoblast C2C12 cells. Sestrin2 supports mitochondrial biogenesis and respiration through control of mitochondrial protein expression and tuning up mitophagy. These discoveries expand our understanding of the potential role of Sestrins in supporting muscle function through mitochondrial signalling.