Physiologic Implications of Reactive Oxygen Species Production by Mitochondrial Complex I Reverse Electron Transport

• Main Authors: John O. Onukwufor (Author), Brandon J. Berry (Author), Andrew P. Wojtovich (Author)
• Format: Book
• Published: MDPI AG, 2019-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2076-3921; 10.3390/antiox8080285
• Keywords: reactive oxygen species; mitochondrial complex I; reverse electron transport; superoxide; hydrogen peroxide; ischemia reperfusion injury; oxidative damage; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 8, Iss 8, p 285 (2019)

Mitochondrial reactive oxygen species (ROS) can be either detrimental or beneficial depending on the amount, duration, and location of their production. Mitochondrial complex I is a component of the electron transport chain and transfers electrons from NADH to ubiquinone. Complex I is also a source of ROS production. Under certain thermodynamic conditions, electron transfer can reverse direction and reduce oxygen at complex I to generate ROS. Conditions that favor this reverse electron transport (RET) include highly reduced ubiquinone pools, high mitochondrial membrane potential, and accumulated metabolic substrates. Historically, complex I RET was associated with pathological conditions, causing oxidative stress. However, recent evidence suggests that ROS generation by complex I RET contributes to signaling events in cells and organisms. Collectively, these studies demonstrate that the impact of complex I RET, either beneficial or detrimental, can be determined by the timing and quantity of ROS production. In this article we review the role of site-specific ROS production at complex I in the contexts of pathology and physiologic signaling.