Mitochondrial Complex II Can Generate Reactive Oxygen Species at High Rates in Both the Forward and Reverse Reactions

Abstract

Background: Complex II is not considered a significant contributor to mitochondrial ROS production. Results: Complex II generates ROS in both the forward reaction, from succinate, and the reverse reaction, from the reduced ubiquinone pool. Conclusion: Occupancy and reduction state of the flavin dictate its ROS producing behavior. Significance: Based on the maximum rates observed, complex II may be a contributor to physiological ROS production.

Salicylic Acid-Dependent Plant Stress Signaling via Mitochondrial Succinate Dehydrogenase

“…S6B), showing that firstly, negative controls without any substrate are essential to determine that any significant signal is not independent of mitochondrial respiration and secondly, that succinate together with SA drives enhanced H 2 O 2 production. This demonstrates that complex II can act as a major source of ROS production with higher rates than complex I,III or alternative NADH dehydrogenases, a phenomenon that has previously be shown in mammalian mitochondria where SDH was found to produce the highest amounts of ROS (Dedkova et al, 2013;Quinlan et al, 2012;Ralph et al, 2011) and recently in barley (Hordeum vulgare) roots, where complex II-derived ROS was shown to be the major source of mitochondrial ROS during mercury toxicity (Tamás and Zelinová, 2017).…”

“…Complex I and III have been long considered to be the major sources of reactive oxygen species (ROS) production inside mitochondria (mtROS), but recent studies in both mammals and plants have demonstrated that complex II can also be a significant source of mtROS (Jardim-Messeder et al, 2015;Quinlan et al, 2012). In mammals, complex II influences reperfusion injury through mtROS production via reverse electron transport after succinate accumulation (Chouchani et al, 2014).…”

Redox homeostasis and age‐related deficits in neuromuscular integrity and function

“…Resting and contracting skeletal muscle produces superoxide via different pathways, and schematic Figures 3 and 4 depict the various sites and mechanisms that have been proposed for RONS generation in skeletal muscle. Briefly, superoxide is generated by the mitochondrial electron transport chain including complex I, complex III76, 77 and, recently, complex II78, 79, 80; the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzymes including NOX2, NOX4, DUOX1 and DUOX255, 56, 59, 81; xanthine oxidase82, 83; and the lipoxygenases (LOXs),84 which are linked to arachidonic acid released by the phospholipase A 2 enzymes85, 86 (for a detailed review, see Ref. [46].…”

Sites of Superoxide and Hydrogen Peroxide Production by Muscle Mitochondria Assessed ex Vivo under Conditions Mimicking Rest and Exercise

“…3). When downstream electron transport is prevented, there is a peak of superoxide/H 2 O 2 production from this site at succinate concentrations close to the physiological range (20), indicating that site II F might also contribute to H 2 O 2 generation at rest. The contribution of site II F during "rest" ex vivo was assessed by adding malonate to inhibit electron transport at this site, followed by correction for consequent changes in the rate of superoxide production from sites I F , III Qo , and I Q .…”

“…1. In order of their maximum capacities, they are as follows: III Qo 4 in complex III (17); I Q (18,19) and II F (20) in complexes I and II; O F , P F , and B F in the 2-oxoglutarate, pyruvate, and branched-chain 2-oxoacid dehydrogenase complexes (16); G Q in mitochondrial glycerol phosphate dehydrogenase (21); I F in complex I (16); E F in ETF/ETF:Q oxidoreductase (22); and D Q in dihydroorotate dehydrogenase (23).…”