Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions.
Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling.
Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6 ; Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada K1A 0K9.
Ryan J
RJ
Mailloux
Toxicology Research Division, Food Directorate, HPFB, Health Canada, Ottawa, Ontario, Canada K1A 0K9.
Xiaolei
X
Jin
Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, Canada K1S 5B6.
William G
WG
Willmore
D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction
D003545:Cysteine
Mitochondria; Redox; S-glutathionylation; S-nitrosylation; S-oxidation