Fig. 3: Mechanisms of autophagy in myocardial I/R injury.

Autophagy is a physiological activity dependent on lysosomal degradation, but excessive autophagy can also lead to cell death. When the injury is mild, activating the autophagy pathway through activating the AMPK/mTOR signaling pathways can protect cardiomyocytes and alleviate myocardial I/R injury. AMPK also acts on OPA1 of mitochondria to improve mitochondrial fusion and alleviate myocardial I/R injury. BNIP3, localized only to mitochondria in cardiomyocytes, can activate the HIF-1α/BNIP3 pathway, increasing Beclin1 and promoting autophagy to protect cardiomyocytes. However, excessive autophagy can cause cardiomyocyte injury when the injury is aggravated. The PI3K/AKT/mTOR pathway is an important signal pathway for downregulating autophagy. The PINK1/Parkin pathway can activate cell autophagy and play an important protective role, but VDAC1 can strongly activate the PINK1/Parkin, inducing excessive autophagy, which can cause cell death. ERS can induce autophagy. PERK/ATF4/CHOP and ATF6/CHOP pathways are activated to induce autophagy after myocardial I/R injury. AMPK AMP-activated protein kinase, OPA1 optic atrophy 1, VDAC1 voltage-dependent anion channel 1, PINK1 PTEN-induced kinase 1, HIF-1α hypoxia-inducible factor-1α, BNIP3 Bcl-2/adenovirus E1B 19-kDa interacting protein 3, PI3K phosphatidylinositol-3-kinase, AKT protein kinase B, ATG13 autophagy-related protein 13, ULK1/2 UNC-51-like kinase 1/2, mTOR mammalian target of rapamycin, FIP200 family interacting protein of 200 kD, LC3II light chain 3 II, PERK protein kinase RNA-like ER kinase, ATF4/6 activating transcription factor 4/6.