fig3

Figure 3. Regulatory mechanisms of mitophagy in ischemic heart disease. Omentin 1 activates PINK1/Parkin-dependent mitophagy by upregulating the SIRT3/FOXO3a signaling pathway. Meanwhile, RhoA also activates this pathway to exert cardioprotective effects. PLK1 overexpression promotes FUNDC1-mediated mitophagy through AMPK activation. Overexpression of JMJD5 activates BNIP3-mediated mitophagy by upregulating HIF-1α, thereby conferring a cardioprotective effect; Mcl-1 also exerts its protective effect by activating this same pathway. Both miR-130a (by inhibiting GJA1) and NR4A can suppress FUNDC1-mediated mitophagy, ultimately leading to myocardial injury. Notch1 inhibits PTEN-PINK1-Parkin signaling-mediated mitophagy. miR-23a inhibits PINK1-Parkin signaling-mediated mitophagy. YTHDF2 inhibits BNIP3 mRNA expression and downregulates mitophagy. IDH3a-K199cr, YTHDF2, PCSK9, and circPOSTN all regulate BNIP3-mediated mitophagy, maintaining mitochondrial homeostasis and conferring cardioprotection. PINK1: PTEN-induced putative kinase protein-1; FOXO3a: forkhead box O3a; SIRT3: sirtuin 3; RhoA: ras homolog family member A; AMPK: AMP-activated protein kinase; FUNDC1: FUN14 domain-containing 1; JMJD5: jumonji-C (JmjC) domain-containing protein 5; HIF1α: hypoxia inducible factor 1 alpha; Mcl-1: myeloid cell leukemia-1; BNIP3: B-cell lymphoma 2 (BCL2) interacting protein 3; GJA1: gap junction protein alpha1; NR4A1: nuclear receptor subfamily 4 group A member 1; PTEN: phosphatase and tensin homolog; IDH3a: isocitrate dehydrogenase 3 alpha subunit; YTHDF2: YTH domain-containing family protein 2; PCSK9: proprotein convertase subtilisin/kexin type 9.