Mitochondrial Lon-induced mitophagy benefits hypoxic resistance via Ca²⁺-dependent FUNDC1 phosphorylation at the ER-mitochondria interface.

ABSTRACT: During hypoxia, FUNDC1 acts as a mitophagy receptor and accumulates at the ER (endoplasmic reticulum)-mitochondria contact sites (EMC), also called mitochondria-associated membranes (MAM). In mitophagy, the ULK1 complex phosphorylates FUNDC1(S17) at the EMC site. However, how mitochondria sense the stress and send the signal from the inside to the outside of mitochondria to trigger mitophagy is still unclear. Mitochondrial Lon was reported to be localized at the EMC under stress although the function remained unknown. In this study, we explored the mechanism of how mitochondrial sensors of hypoxia trigger and stabilize the FUNDC1-ULK1 complex by Lon in the EMC for cell survival and cancer progression. We demonstrated that Lon is accumulated in the EMC and associated with FUNDC1-ULK1 comple

SUBMITTER: Ponneri Babuharisankar A 

PROVIDER: S-EPMC10020552 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature