Mitochondrial Drp1 recognizes and induces excessive mPTP opening after hypoxia through BAX-PiC and LRRK2-HK2

• DOI: 10.1038/s41419-021-04343-x
• Publication Date: 2021-11-05T13:03:14Z
• Authors: Chenyang Duan; Lei Kuang; Chen Hong; Xinming Xiang; Jiancang Liu; Qinghui Li; Xiaoyong Peng; Yuanqun Zhou; Hongchen Wang; Liangming Liu; Tao Li
• Keywords: MPTP; PINK1; Mitochondrial apoptosis-induced channel; DNAJA3; DNM1L; Hypoxia

Abstract Mitochondrial mass imbalance is one of the key causes cardiovascular dysfunction after hypoxia. The activation dynamin-related protein 1 (Drp1), as well its mitochondrial translocation, play important roles in changes both morphology and functions However, addition to mediating fission, whether Drp1 has other regulatory homeostasis translocation unknown. In this study, we performed a series interaction colocalization assays found that, may promote excessive opening permeability transition pore (mPTP) Firstly, maximumly recognizes mPTP channels by binding Bcl-2-associated X (BAX) phosphate carrier (PiC) mPTP. Then, leucine-rich repeat serine/threonine-protein kinase 2 (LRRK2) recruited, whose activity inhibited direct with Subsequently, mPTP-related hexokinase (HK2) inactivated at Thr-473 dissociates from membrane, ultimately causing structural disruption overopening mPTP, which aggravates cellular Thus, our study interprets dual regulation on hypoxia proposes new fission-independent mechanism for role hypoxic injury.