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. 2021 Jan 13;49(1):485–494. doi: 10.1042/BST20200981

Figure 1. VCP's effects on cardiac ischemia/reperfusion injury.

Figure 1.

The decreased VCP in ischemia reperfusion leads to a decrease in the physically interaction of VCP with Akt and the activation of NF-kB and STAT3 in cardiomyocytes, NF-kB and STAT3 are the transcriptional factors of iNOS, which has been proven to improve the respiratory function of mitochondria. In addition, the physically association of VCP, MICU1, and Parkin decreased, which reduced the degradation of MICU1, resulting in the continuous opening of mitochondrial permeability transition pore, calcium overload and decreased respiratory function in the mitochondria. Therefore, the decline of iNOS and the respiratory function of mitochondria jointly promote the cardiac dysfunction under ischemia–reperfusion. The overexpression of VCP enhances the interaction of VCP and Akt, which results in an increase in NF-kB and STAT3 into the nuclear, and the production of iNOS, thereby enhancing the mitochondrial respiratory function of cardiomyocytes. Meanwhile, the physically interaction of VCP, MICU1 and Parkin is enhanced under conditions of VCP/p97 overexpression, which accelerates the degradation of MICU1, reduces the opening frequency of mitochondrial permeability transition pore, and inhibits mitochondrial calcium overload. Thus the increase in iNOS production and the improvement of mitochondrial respiratory function together protect the cardiac dysfunction under ischemia–reperfusion.