Histone deacetylase-mediated regulation of endolysosomal pH.

ABSTRACT: The pH of the endolysosomal system is tightly regulated by a balance of proton pump and leak mechanisms that are critical for storage, recycling, turnover, and signaling functions in the cell. Dysregulation of endolysosomal pH has been linked to aging, amyloidogenesis, synaptic dysfunction, and various neurodegenerative disorders, including Alzheimer's disease. Therefore, understanding the mechanisms that regulate luminal pH may be key to identifying new targets for managing these disorders. Meta-analysis of yeast microarray databases revealed that nutrient-limiting conditions inhibited the histone deacetylase (HDAC) Rpd3 and thereby up-regulated transcription of the endosomal Na⁺/H⁺ exchanger Nhx1, resulting in vacuolar alkalinization. Consistent with these findings,

SUBMITTER: Prasad H 

PROVIDER: S-EPMC5936830 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature