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Downregulated NDUFA13, an accessory subunit of complex I, has been shown to be able to render the tumor cells more resistant to apoptosis. In the present study, therefore, we aimed to investigate whether and how NDUFA13 downregulation in the heart protects against I/R injury.
We generated Myh6Cre+ERTamNDUFA13flox/flox mice and demonstrated that heterozygous NDUFA13 knockout, i.e. Myh6Cre+ERTamNDUFA13flox/- mice exhibited normal cardiac morphology and function at normal state, and were more resistance to apoptosis when exposed to ischemia-reperfusion (I/R) injury, resulting in a significant decrease in infarct size (IS).
Interestingly, a decrease in substrate driven oxygen consumption of complex I was observed, however, a compensation for the total oxygen consumption by complex I and complex II was observed, which was associated with an increase in residual oxygen consumption (ROX) when complex III inhibitor, Antimycin A, was used. Interestingly, less superoxide generation was observed in heterozygous knockout mice compared with normal control, which may attenuate the injury caused by ischemia reperfusion.
In conclusion, heterozygous NDUFA13 knockout attenuated infarct size after ischemia reperfusion through reduced superoxide production in mitochondria.