Abstract
Recent evidence suggests that mitochondrial complex II is an essential mediator of myocardial ischemia–reperfusion injury. The present study aimed to investigate the effects of fatty acid supplementation or high-fat diet (HFD) on cardiac mitochondrial activity. The changes of complex I and complex II activities and mitochondrial oxygen consumption rate (OCR) following hypoxia and re-oxygenation under these conditions were studied. Our results have shown that OCR (mitochondrial activity) was significantly increased with palmitoylcarnitine supplementation in mitochondria-enriched fraction from C57BL/6 mice hearts. Mitochondrial complex I activity was unaffected by palmitoylcarnitine but complex II activity was enhanced. Re-oxygenation following 30-min hypoxia transiently increased OCR but such an effect on OCR was abolished by complex II inhibitor, malonate, but not by complex I inhibitor, rotenone, despite that complex I activity was significantly increased with re-oxygenation following hypoxia in the presence of palmitoylcarnitine. Furthermore, OCR and complex II activity were significantly increased in the mitochondria from high-fat diet mice heart compared with those of normal or low-fat diet mice. Re-oxygenation to mitochondria following 30-min hypoxia increased OCR in all three groups but significantly more in HFD. Malonate abolished re-oxygenation-induced OCR increment in all groups. Our results indicate that complex II activity and OCR are enhanced with palmitoylcarnitine or in HFD mice heart. Although re-oxygenation following hypoxia enhanced complex II and complex I activities, complex II plays an important role in increasing mitochondrial activity, which may be instrumental in myocardial injury following ischemic reperfusion.
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Funding
This work was financially supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2019R1A2C1005720) and National Natural Science Foundation of China (NSFC 31660284, NSFC31860288).
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Procedures involving animals were performed in accordance with the UK Home Office Guidance on the operation of the Animals (Scientific Procedures) Act 1986 and also conform to the Institutional Animal Care and Use Committee (IACUC) in Seoul National University (IACUC approval no.: SNU-101213-1;SNU-160119-4-6).
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Zhu, S.C., Chen, C., Wu, Y.N. et al. Cardiac complex II activity is enhanced by fat and mediates greater mitochondrial oxygen consumption following hypoxic re-oxygenation. Pflugers Arch - Eur J Physiol 472, 367–374 (2020). https://doi.org/10.1007/s00424-020-02355-8
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DOI: https://doi.org/10.1007/s00424-020-02355-8