The protective effects of selenium on mitochondrial quality under exogenous and endogenous stressors.

Selenium (Se) and selenoproteins play a significant role in preventing mitochondrial damage. Se regulates mitochondrial dynamics, biogenesis, and mitophagy, but the mechanisms by which it controls mitochondrial quality remain to be fully characterized. Thus, the objective of this review is to address the underlying mechanisms of Se in regulation of mitochondrial quality control upon exposure to endogenous and exogenous stressors. Contemporary data show that Se deficiency is associated with a shift from mitochondrial fusion to fission, inhibition of mitochondrial biogenesis via down-regulation of sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/nuclear respiratory factor 1 and 2 (NRF1/2)/mitochondrial transcription factor A (TFAM) signaling, and alterations in PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy in vitro and in vivo. The role of Se in regulating mitochondrial quality control is mediated by specific selenoproteins, as evidenced from experimental selenoprotein knockout and overexpression models. Correspondingly, treatment with various forms of Se attenuates inhibitory effect of endogenous stressors (oxidative stress, ischemia, etc.), as well as exogenous agents like heavy metals, ammonia, fluoride, mycotoxins, and paraquat, on mitochondrial fusion/fission balance and biogenesis. Administration of Se mitigates the adverse effects of these stressors on mitophagy by recovering impaired mitophagy or by inhibiting mitophagy overactivation. Therefore, Se treatment might be considered a therapeutic approach to mitigate the adverse effects of various stressors on mitochondrial quality control and functioning, leading to prevention of liver, kidney, brain, and intestinal damage. However, the specific mechanisms, as well as dose-response and species-specific effects have yet to be investigated.