PXD037896

PXD037896 is an original dataset announced via ProteomeXchange.

Title	Multilevel changes in the Mevalonate Pathway in Reduced Autophagy Aging Skeletal Muscle Cell Models
Description	Autophagy is an essential cellular pathway that maintains homeostasis in the cell and healthy function overtime. Decline in autophagy function with age has been observed in skeletal muscle which leads to deterioration of muscle function. Defective autophagy has been linked with a reduction in the post-translational protein of prenylation bringing into question the association defective autophagy has with the mevalonate pathway. In this work, cell models of reduced autophagy function in L6 rat myoblast cells were used to study the response of cells to reduced autophagy with a focus on the mevalonate pathway and protein prenylation. The first cell model was an ATG7 knockout produced using CRISPR/Cas9 to remove the expression of functional ATG7 protein. The second cell model was an ATG7 siRNA treatment to reduce the expression of ATG7 protein. Mass spectrometry was applied to study the expression changes of prenylated proteins with enrichment for prenylated proteins by an isoprenoid analog. Gene expression of prenylated proteins and enzymes in the mevalonate pathway was assessed using quantitative polymerase chain reaction. Overall prenylation function was evaluated using mass cytometry with an isoprenoid analog and reporter attached using copper catalyzed cycloaddition. Both cell models indicated a direct impact on the mevalonate pathway related to autophagy decline, but there were differences between the two models. These cell models provide key findings that autophagy and the mevalonate pathway are interconnected at the gene, protein and functional level, in skeletal muscle indicating an area to target for further study in the understanding of the aging phenotype.
HostingRepository	PRIDE
AnnounceDate	2026-02-12
AnnouncementXML	Submission_2026-02-11_22:15:51.171.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuanzhe Chen
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	farnesylated residue; TMT6plex-126 reporter+balance reagent acylated residue; biotinylated residue; geranylgeranylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-11-03 04:06:53	ID requested
⏵ 1	2026-02-11 22:15:51	announced

10.1021/JACS.5C19824;

submitter keyword: Prenyaltion, ATG7, Prenylomics, Autophagy,Proteomics, mevalonate pathway

Mark D Distefano
contact affiliation	Chemistry Department, University of Minnesota, United States
contact email	diste001@umn.edu
lab head
Yuanzhe Chen
contact affiliation	University of Minnesota
contact email	chen6980@umn.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037896
     1. Label: PRIDE project
     2. Name: Multilevel changes in the Mevalonate Pathway in Reduced Autophagy Aging Skeletal Muscle Cell Models