Figure 2.

Diagram illustrating mitochondria redox homeostasis. Events involved in ROS generation and anti-oxidant defense are marked with red and green stars, respectively. Proteins taking part in pro- and anti-oxidant events are symbolized in 'red' and 'blue', respectively. Proteins playing non-oxidative roles are marked with 'grey'. Mitochondrial enzymes known to generate ROS include pyruvate dehydrogenase (PDH), aconitase (ACO), α-ketoglutarate dehydrogenase (KGDH), electron transport chain complex I (ETC-I) to III (ETC-III), glycerol-3-phosphate dehydrogenase (GPDH), dihydroorotate dehydrogenase (DHOH), monoamine oxidase (MAO), cytochrome b5 reductase (B5R). When these enzymes are abundantly charged and the mitochondrial membrane potential is high, electrons are transferred to oxygen towards ROS generation. Mitochondria also contain a large anti-oxidant defense system to maintain the ROS balance in mitochondria. Non-enzymatic components of this anti-oxidant system include α-tocopherol (αTCP), coenzyme Q10 (Q10), cytochrome C (cytoC) and glutathione (GSH), which are symbolized using 'light blue'. Enzymatic components include manganese superoxide dismutase (MnSOD), catalase (Cat), glutathione peroxidase (GPX), phospholipid hydroperoxide glutathione peroxidase (PGPX), glutathione reductase (GR), peroxiredoxins (PRX3/5), glutaredoxin (GRX2), thioredoxin (TRX2), and thioredoxin reductase (TRXR2), isocitrate dehydrogenase (IDH), malic enzyme (ME) and nicotinamide nucleotide transhydrogenase (NNTH), which are represented in 'dark blue'. When mitochondria redox homeostasis is perturbed, net ROS is produced that can damage mitochondria, leading to decreased anti-oxidant ability and increased ROS generation that can further damage mitochondria (panel B). Additional annotations: GSSG, glutathione disulfide; LOH, lipid hydroxide; LOOH, lipid hydroperoxide; o, oxidized state; r, reduced state. This figure is redrawn and adapted with permission from ¹³.