TRPML3/BK complex promotes autophagy and bacterial clearance by providing a positive feedback regulation of mTOR via PI3P.

ABSTRACT: TRPML3 is a Ca²⁺/Na⁺ release channel residing in both phagophores and endolysosomal membranes. It is activated by PI3P and PI3,5P2. Its activity can be enhanced by high luminal pH and by replacing luminal Na⁺ with K⁺. Here, we report that big-conductance Ca²⁺-activated potassium (BK) channels form a positive feedback loop with TRPML3. Ca²⁺ release via TRPML3 activates BK, which in turn facilitates TRPML3-mediated Ca²⁺ release, potentially through removing luminal Na⁺ inhibition. We further show that TRPML3/BK and mammalian target of rapamycin (mTOR) form another positive feedback loop to facilitate autophagy induction in response to nutrient starvation, i.e., mTOR inhibition upon nutrient starvation act

SUBMITTER: Xu M 

PROVIDER: S-EPMC10450854 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature