Lysosomal targetomics of ghr KO mice shows chaperone-mediated autophagy degrades nucleocytosolic acetyl-coA enzymes.

ABSTRACT: Mice deficient in GHR (growth hormone receptor; ghr KO) have a dramatic lifespan extension and elevated levels of hepatic chaperone-mediated autophagy (CMA). Using quantitative proteomics to identify protein changes in purified liver lysosomes and whole liver lysates, we provide evidence that elevated CMA in ghr KO mice downregulates proteins involved in ribosomal structure, translation initiation and elongation, and nucleocytosolic acetyl-coA production. Following up on these initial proteomics findings, we used a cell culture approach to show that CMA is necessary and sufficient to regulate the abundance of ACLY and ACSS2, the two enzymes that produce nucleocytosolic (but not mitochondrial) acetyl-coA. Inhibition of CMA in NIH3T3 cells has been shown to lead to aberrant acc

SUBMITTER: Endicott SJ 

PROVIDER: S-EPMC9298451 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature