Targeting mitochondrial metabolic and redox status to treat ischaemia/reperfusion injury

Ischaemia/reperfusion (I/R) injury underlies many pathologies, including myocardial infarction (MI) and stroke, which account for more than a third of overall mortality in the UK.

Furthermore, even for those who survive the initial I/R event in the heart the subsequent chronic heart failure becomes a major disease burden for society. Despite many attempts, there are no clinically approved therapies that protect the heart against I/R injury.

We want to understand how I/R injury occurs so we can find new, effective drug targets and translate these interventions to the clinic as novel therapies.

This proposal builds on our recent ground-breaking work that showed I/R injury is a precise process that arises due to predictable changes in mitochondrial metabolic and redox status. This breakthrough now enables us to develop new classes of rational therapies.

Here we describe how we will investigate the role of mitochondria in I/R injury, in order to understand the underlying mechanisms and ultimately develop new therapies as the next step in translation to the clinic.