Fig. 5: The schematic diagram showing the mechanisms of mitochondrial Drp1 recognizing and inducing excessive mPTP opening after hypoxia.

Hypoxia-activated mitochondrial Drp1 firstly recognizes mPTP channels through binding with its structural proteins, BAX and PiC, then recruits LRRK2 to mitochondrial contraction or fission sites and blocks its kinase activity site (LRRK2 G2019), leading to the dephosphorylation and mitochondrial separation of mPTP related protein HK2, resulting in structural damage and excessive opening of mPTP channel after hypoxia.