Computationally modeling mammalian succinate dehydrogenase kinetics identifies the origins and primary determinants of ROS production.

ABSTRACT: Succinate dehydrogenase (SDH) is an inner mitochondrial membrane protein complex that links the Krebs cycle to the electron transport system. It can produce significant amounts of superoxide ([Formula: see text]) and hydrogen peroxide (H₂O₂); however, the precise mechanisms are unknown. This fact hinders the development of next-generation antioxidant therapies targeting mitochondria. To help address this problem, we developed a computational model to analyze and identify the kinetic mechanism of [Formula: see text] and H₂O₂ production by SDH. Our model includes the major redox centers in the complex, namely FAD, three iron-sulfur clusters, and a transiently bound semiquinone. Oxidation state transitions involve a one- or two-electron redox reacti

SUBMITTER: Manhas N 

PROVIDER: S-EPMC7650251 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature