First, we did not determine the mechanisms by which I/R downregulates Psmb8 expression in cardiomyocytes; which specific E3 ligases promote Drp1 ubiquitination for degradation by Psmb8; how Psmb8 increases Mfn1 and Mfn2 expression in cardiomyocytes, or whether the activation of Psmb8 represents a therapeutic strategy for ischaemic heart disease in human patients. The gene discussed is MFN2; the disease is heart disorder.