Complexities of complex II: Sulfide metabolism in vivo

Gary Cecchini

doi:10.1016/j.jbc.2022.101661

Abstract

High levels of H2S produced by gut microbiota can block oxygen utilization by inhibiting mitochondrial complex IV. Kumar et al. have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport. The reverse activity of mitochondrial complex II (succinate-quinone oxidoreductase, i.e., fumarate reduction) generates oxidized coenzyme Q, which is then reduced by the mitochondrial sulfide quinone oxidoreductase to oxidize H2S. This newly identified redox circuitry points to the importance of complex II reversal in mitochondria during periods of hypoxia and cellular stress.

Highlights

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record
sulfide quinone oxidoreductase (SQOR) and complex II are flavoproteins that are bound to the inner mitochondrial membrane, and both enzymes reduce coenzyme Q (CoQ) in their normal physiological activities
The approach of Kumar et al [3] used a variety of methodologies, including nanodiscembedded SQOR, ectopic expression of enzymes to manipulate the NAD+/NADH ratio and the products of the malate-aspartate shuttle in cell lines, metabolomics, shRNA knockdown of expression of enzymes involved in CoQ reduction, and knockdown of the flavoprotein subunit of complex II (SDHA) in mouse models

Summary

Introduction

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. Kumar et al have shown how cells respond to this inhibition by using the mitochondrial sulfide oxidation pathway and reverse electron transport.

Results

Conclusion