Use of S1QELs and S3QELs to link mitochondrial sites of superoxide and hydrogen peroxide generation to physiological and pathological outcomes.

Abstract:

:Changes in mitochondrial superoxide and hydrogen peroxide production may contribute to various pathologies, and even aging, given that over time and in certain conditions, they damage macromolecules and disrupt normal redox signalling. Mitochondria-targeted antioxidants such as mitoQ, mitoVitE, and mitoTEMPO have opened up the study of the importance of altered mitochondrial matrix superoxide/hydrogen peroxide in disease. However, the use of such tools has caveats and they are unable to distinguish precise sites of production within the reactions of substrate oxidation and the electron transport chain. S1QELs are specific small-molecule Suppressors of site IQElectron Leak and S3QELs are specific small-molecule Suppressors of site IIIQoElectron Leak; they prevent superoxide/hydrogen production at specific sites without affecting electron transport or oxidative phosphorylation. We discuss the benefits of using S1QELs and S3QELs as opposed to mitochondria-targeted antioxidants, mitochondrial poisons, and genetic manipulation. We summarise pathologies in which site IQ in mitochondrial complex I and site IIIQo in mitochondrial complex III have been implicated using S1QELs and S3QELs.

journal_name

Biochem Soc Trans

authors

Watson MA,Wong HS,Brand MD

doi

10.1042/BST20190305

subject

Has Abstract

pub_date

2019-10-31 00:00:00

pages

1461-1469

issue

5

eissn

0300-5127

issn

1470-8752

pii

BST20190305

journal_volume

47

pub_type

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