Reduced endosomal microautophagy activity in aging associates with enhanced exocyst-mediated protein secretion.

ABSTRACT: Autophagy is essential for protein quality control and regulation of the functional proteome. Failure of autophagy pathways with age contributes to loss of proteostasis in aged organisms and accelerates the progression of age-related diseases. In this work, we show that activity of endosomal microautophagy (eMI), a selective type of autophagy occurring in late endosomes, declines with age and identify the sub-proteome affected by this loss of function. Proteomics of late endosomes from old mice revealed an aberrant glycation signature for Hsc70, the chaperone responsible for substrate targeting to eMI. Age-related Hsc70 glycation reduces its stability in late endosomes by favoring its organization into high molecular weight protein complexes and promoting its internalization/degradation in

SUBMITTER: Krause GJ 

PROVIDER: S-EPMC9577956 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature