Fig. 4

Effects of Drp1 on mitophagy are closely related to the degree of ischemia and hypoxia. a Moderate ischemia/hypoxia-induced compensatory mitochondrial damage. In moderate ischemia/hypoxia, AMPK activates ULK1 and phosphorylates Rab9 at Ser179, which promotes the association between Rab9 and RIP1, followed by Drp1 phosphorylation at Ser616. Damaged mitochondria are sequestered by autophagosomes derived from the trans-Golgi network. b Severe ischemia/hypoxia-induced decompensated mitochondrial damage. In severe ischemia/hypoxia, mitochondrial Drp1 recruits LRRK2, thereby preventing Parkin translocation and reducing the encapsulation and degradation of damaged mitochondria by autophagosomes. Drp1 Dynamin-related protein 1, AMPK adenosine monophosphate-activated protein kinase, ULK1 unc-51-like kinase 1, LRRK2 leucine-rich repeat kinase 2, LC3-II microtubule-associated protein 1B-light chain 3, Ub ubiquitin, PINK1 PTEN-induced kinase 1, ROS reactive oxygen species, FUNDC1 FUN14 domain-containing protein 1, RIP1 receptor interacting protein 1, mPTP mitochondrial permeability transition pore, Cyt C cytochrome C