PXD023309

PXD023309 is an original dataset announced via ProteomeXchange.

Title	Lysosomal targetomics in ghrKO mice reveals a role for chaperone-mediated autophagy in shaping the nucleocytosolic acetyl-coA production pathway
Description	Mice deficient for growth hormone receptor (ghrKO) have a dramatic lifespan extension, through an unknown mechanism. Compared to normal littermates,ghrKO mice have 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 ghrKO mice specifically downregulates proteins involved in ribosomal structure, translation initiation and elongation, and nucleocytosolic acetyl-coA production. Using a combination of cell culture and mouse models, we show that CMA is both necessary and sufficient to regulate the abundance of ACLY and ACSS2, the two enzymes that produce nucleocytosolic (but not mitochondrial) acetyl-coA. Degradation of ACLY and ACSS2 by CMA prevents aberrant accumulation of lipid droplets in NIH3T3 cells. Nucleocytosolic acetyl-coA has been implicated in longevity. Elevated CMA in ghrKO mice might contribute to their long lifespan by diminishing nucleocytoplasmic acetyl-coA availability.
HostingRepository	PanoramaPublic
AnnounceDate	2020-12-24
AnnouncementXML	Submission_2020-12-24_19:13:54.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Michael MacCoss
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	Carbamidomethyl
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-12-24 10:41:38	ID requested
⏵ 1	2020-12-24 19:13:55	announced

Dataset with its publication pending

submitter keyword: Aging, Chaperone-mediated autophagy, Endocrine regulation of autophagy, Endocrine regulation of aging, Acetyl-coA metabolism

Richard A. Miller
contact affiliation	University of Michigan, Department of Pathology, Ann Arbor, MI
contact email	millerr@umich.edu
lab head
Michael MacCoss
contact affiliation	University of Washington, Department of Genome Sciences, Seattle, WA
contact email	maccoss@uw.edu
dataset submitter

Panorama Public dataset URI