Collapse of late endosomal pH elicits a rapid Rab7 response via V-ATPase and RILP.

ABSTRACT: Endosomal-lysosomal trafficking is accompanied by the acidification of endosomal compartments by the H⁺-V-ATPase to reach low lysosomal pH. Disruption of proper pH impairs lysosomal function and the balance of protein synthesis and degradation (proteostasis). We used the small dipeptide LLOMe, which is known to permeabilize lysosomal membranes, and find that LLOMe also impacts late endosomes (LEs) by neutralizing their pH without causing membrane permeabilization. We show that LLOMe leads to hyper-activation of Rab7 and disruption of tubulation and mannose-6-phosphate receptor (CI-M6PR) recycling on pH-neutralized LEs. Either pH neutralization (NH₄Cl) or Rab7 hyper-active mutants alone can phenocopy the alterations in tubulation and CI-M6PR trafficking. Mechanisticall

SUBMITTER: Mulligan RJ 

PROVIDER: S-EPMC10634777 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature