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PXD023309 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleLysosomal targetomics in ghrKO mice reveals a role for chaperone-mediated autophagy in shaping the nucleocytosolic acetyl-coA production pathway
DescriptionMice 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.
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMichael MacCoss
SpeciesList scientific name: Mus musculus; NCBI TaxID: 10090;
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-12-24 10:41:38ID requested
12020-12-24 19:13:55announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Aging, Chaperone-mediated autophagy, Endocrine regulation of autophagy, Endocrine regulation of aging, Acetyl-coA metabolism
Contact List
Richard A. Miller
contact affiliationUniversity of Michigan, Department of Pathology, Ann Arbor, MI
contact emailmillerr@umich.edu
lab head
Michael MacCoss
contact affiliationUniversity of Washington, Department of Genome Sciences, Seattle, WA
contact emailmaccoss@uw.edu
dataset submitter
Full Dataset Link List
Panorama Public dataset URI