Disorders of lysosomal acidification-the emerging role of v-ATPase in aging and neurodegenerative disease.

Disorders of lysosomal acidification-the emerging role of v-ATPase in aging and neurodegenerative disease.
Ageing Res Rev. 2016 May 16;
Authors: Colacurcio DJ, Nixon RA
Abstract
Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longevity, and adult-onset neurodegenerative diseases, including forms of Parkinson Disease and Alzheimer Disease. Genetic defects of subunits composing the v-ATPase or v-ATPase-related proteins occur in an increasingly recognized group of familial neurodegenerative diseases. Here, we review the expanding roles of the v-ATPase complex as a platform regulating lysosomal proteolysis and cellular homeostasis. We discuss the unique vulnerability of neurons to persistent low level lysosomal dysfunction and review recent clinical and experimental studies that link dysfunction of the v-ATPase complex to neurodegenerative diseases across the age spectrum.
PMID: 27...

Source: Ageing Research Reviews - May 15, 2016 Category: Genetics & Stem Cells Authors: Colacurcio DJ, Nixon RA Tags: Ageing Res Rev Source Type: research