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Professor Andrew Halestrap

Professor Andrew Halestrap

Professor Andrew Halestrap
MA(Cantab), PhD, DSc(Bristol), FMedSci

Senior Research Fellow in Biochemistry

Emeritus Professor

Area of research

Mitochondria and cell death; monocarboxylate (lactate) transporters

Office 65 St Michaels Hill Room 2.4
Biomedical Sciences Building,
University Walk, Clifton BS8 1TD
(See a map)

+44 (0) 117 331 2118

Summary

The mechanism of the mitochondrial permeability transition and its role in heart reperfusion injury:

In conditions such as ischaemic heart disease and stroke, mitochondria experience oxidative stress and become overloaded with Ca2+. This leads to the opening of a non-specific pore in the inner mitochondrial membrane, the mitochondrial permeability transition pore (MPTP), that destroys the functional integrity of mitochondria and leads to cell death. It can be inhibited by the immunosuppressant drugs Cyclosporin A and Sanglifehrin A.

We are studying the molecular mechanism of the MPTP and how its inhibition can protect the hearts from the damaging effects of ischaemia and reperfusion. One potent protective mechanism involves exposing hearts to brief ischaemic episodes prior to prolonged ischemia and we are investigating how this effect is mediated with a particular emphasis on the role of reactive oxygen species.

Monocarboxylate transportMolecular model of MCT1 cross-linked by an inhibitor (DIDS) to its ancillary protein embigin

Lactic acid transport across the plasma membrane is essential in both glycolytic cells such as muscle and tumour, and also in the heart and liver, which utilise lactic acid. Fourteen distinct proton-linked monocarboxylate transporters (MCTs) have been described, each with a characteristic tissue distribution and role. An ancillary glycoprotein, basigin or embigin, is required for expression of MCT1 and MCT4 at the cell surface. Structure/function studies of MCTs and basigin are being undertaken by site-directed mutagenesis and molecular modeling, with the goal of developing isoform-specific inhibitors that may be effective chemotherapeutic agents for the treatment of cancer.

We are also seeking to identify the mammalian mitochondrial pyruvate carrier, that plays a central role in carbohydrate and fat metabolism.

Memberships

Organisations

School of Biochemistry

Other sites

Recent publications

View complete publications list in the University of Bristol publications system

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