The intracellular Ca²⁺ channel TRPML3 is a PI3P effector that regulates autophagosome biogenesis.

ABSTRACT: Autophagy is a multiple fusion event, initiating with autophagosome formation and culminating with fusion with endo-lysosomes in a Ca²⁺-dependent manner. The source of Ca²⁺ and the molecular mechanism by which Ca²⁺ is provided for this process are not known. The intracellular Ca²⁺ permeable channel transient receptor potential mucolipin 3 (TRPML3) localizes in the autophagosome and interacts with the mammalian autophagy-related protein 8 (ATG8) homolog GATE16. Here, we show that lipid-regulated TRPML3 is the Ca²⁺ release channel in the phagophore that provides the Ca²⁺ necessary for autophagy progress. We generated a TRPML3-GCaMP6 fusion protein as a targeted reporter of TRPML3 compartment localization and channel function.

SUBMITTER: Kim SW 

PROVIDER: S-EPMC9618060 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature