Rapid mitochondrial repolarization upon reperfusion after cardiac ischemia

The results of a collaborative research study jointlyled  Mike Murphy’s laboratory have been published in Nature Cardiovascular Research.

In the research article, scientists at the MBU and the Department of Medicine, University of Cambridge and the National Heart, Lung and Blood Institute (NHLBI), NIH, Bethesda, USA explain findings that expand their understanding of ischemia-reperfusion injury:

The mitochondrial membrane potential drives oxidative phosphorylation and alterations contribute to cardiac pathologies, but real-time assessment of ΔΨm has not been possible. Here they describe noninvasive measurements using mitochondrial haem absorbances, which rapidly respond to mitochondrial membrane potential. Multi-wavelength absorbance spectroscopy enabled their continuous monitoring in isolated mitochondria and the perfused heart. Calibration of haem  absorbance in isolated mitochondria enabled estimation of mitochondrial membrane potential in the heart during ischemia–reperfusion injury, an unknown limiting the understanding of ischemia–reperfusion injury. In perfused hearts, mitochondrial membrane potential declined during ischaemia and rapidly reestablished upon reperfusion, supported by oxidation of the succinate accumulated during ischaemia. These findings expand our understanding of ischemia–reperfusion injury.

Publication reference:

Giles, A.V., Covian, R., Prag, H.A. et al. Rapid mitochondrial repolarization upon reperfusion after cardiac ischemia. Nat Cardiovasc Res (2025). https://doi.org/10.1038/s44161-025-00752-9

LEGEND

Real-time determination of mitochondrial membrane potential in the intact mouse heart. a, Transmural absorbance was determined by introducing a light catheter into the left ventricle of the isolated mouse heart and collecting the light transmitted across the heart wall using an integrating sphere. b, The isolated heart was subjected to global no-flow ischaemia followed by reperfusion and the redox poise of the b-type haems determined by multi-wavelength absorbance spectroscopy. Mitochondrial membrane potential was calculated over time using the calibration curve generated in isolated mitochondria.