Understanding and preventing mitochondrial oxidative damage.

TitleUnderstanding and preventing mitochondrial oxidative damage.
Publication TypeJournal Article
Year of Publication2016
AuthorsMurphy, MP
JournalBiochem Soc Trans
Volume44
Issue5
Pagination1219-1226
Date Published2016 Oct 15
ISSN1470-8752
Abstract

Mitochondrial oxidative damage has long been known to contribute to damage in conditions such as ischaemia-reperfusion (IR) injury in heart attack. Over the past years, we have developed a series of mitochondria-targeted compounds designed to ameliorate or determine how this damage occurs. I will outline some of this work, from MitoQ to the mitochondria-targeted S-nitrosating agent, called MitoSNO, that we showed was effective in preventing reactive oxygen species (ROS) formation in IR injury with therapeutic implications. In addition, the protection by this compound suggested that ROS production in IR injury was mainly coming from complex I. This led us to investigate the mechanism of the ROS production and using a metabolomic approach, we found that the ROS production in IR injury came from the accumulation of succinate during ischaemia that then drove mitochondrial ROS production by reverse electron transport at complex I during reperfusion. This surprising mechanism led us to develop further new therapeutic approaches to have an impact on the damage that mitochondrial ROS do in pathology and also to explore how mitochondrial ROS can act as redox signals. I will discuss how these approaches have led to a better understanding of mitochondrial oxidative damage in pathology and also to the development of new therapeutic strategies.

DOI10.1042/BST20160108
Alternate JournalBiochem. Soc. Trans.
Citation Key10.1042/BST20160108
PubMed ID27911703
PubMed Central IDPMC5095902
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom