Fig. 2 |. Mitochondrial quality control.

The mitochondrial quality control system consists of molecular and organelle quality control mechanisms. Protein quality control is maintained by chaperones that catalyse protein folding and ATP-dependent proteases that remove unwanted and damaged proteins. In settings where the capacity of protein quality control is overwhelmed, the mitochondrial unfolded protein response (UPR^mt) is induced. In this response, signals released from mitochondria trigger the transcription of nuclear genes that encode mitochondrial chaperones to enhance the protein-folding capacity. The mitochondrial antioxidant defence system consisting of superoxidase dismutases (SODs), glutathione peroxidases (GPXs) and peroxiredoxin limits reactive oxygen species (ROS) levels within the organelles and the DNA damage repair machinery repairs damaged mitochondrial DNA. When these molecular quality control mechanisms fail to restore mitochondrial homeostasis, organelle quality control mechanisms are activated. Mitochondrial fusion mediated by mitofusin 1 (MFN1), MFN2 and dynamin-like 120 kDa protein, mitochondrial (OPA1) mitigates organelle stress by enabling the contents of damaged mitochondria to be combined with those of healthy mitochondria for complementation. Fission, which is regulated by cytosolic dynamin-1-like protein (DRP1) and its receptors, segregates damaged parts of the mitochondrial network, which are then removed by mitophagy. Mitophagy is mediated by the serine/threonine-protein kinase PINK1, mitochondrial (PINK1)–parkin pathway and mitophagy receptors, including BCL-2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), BCL-2-interacting protein 3-like and FUN14 domain-containing 1 (FUNDC1). Mitochondrial biogenesis depends on specific transcription factors, including peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α). When mitochondrial damage exceeds the capacity of mitochondria quality control or when mitochondrial quality control is defective, cell death ensues. MOMP, mitochondrial outer membrane permeabilization.