PXD036980

PXD036980 is an original dataset announced via ProteomeXchange.

Title	DNA damage response signaling to mitochondria drives senescence
Description	Cellular senescence is a stress-induced permanent cell cycle arrest typically accompanied by expression of the cyclin-dependent kinase inhibitor p16. Recent studies have suggested that p16-expressing senescent cells accumulate in the body with age and play a causative role in aging. Various stresses, such as telomere shortening and oncogene activation, induce cellular senescence by generating DNA damage. However, how DNA damage leads to p16 expression is incompletely understood. We identified BNIP3 in a genome-wide siRNA screen for genes involved in p16 expression upon DNA damage. Mass spectrometric analysis of BNIP3-binding proteins yielded the DDR kinase ATM and components of the mitochondrial contact site and cristae organizing system (MICOS) complex. We found that BNIP3 increases the number of mitochondrial cristae upon DNA damage by electron microscopy. Metabolomic analysis linked BNIP3 to altered acetyl-CoA metabolism during DNA damage-induced senescence. We found that BNIP3 facilitates the oxidation of fatty acids to acetyl-CoA, an acetyl group donor, and promotes histone acetylation around the p16 gene and associated p16 expression. Our findings suggest that DDR signaling to mitochondria via BNIP3 promotes p16 expression through fatty acid oxidation and histone acetylation.
HostingRepository	PRIDE
AnnounceDate	2025-01-14
AnnouncementXML	Submission_2025-01-13_20:48:00.344.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD036980
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Shota Yamauchi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-25 14:35:13	ID requested
⏵ 1	2025-01-13 20:48:01	announced

10.1126/sciadv.ado5887;

10.6019/PXD036980;

Yamauchi S, Sugiura Y, Yamaguchi J, Zhou X, Takenaka S, Odawara T, Fukaya S, Fujisawa T, Naguro I, Uchiyama Y, Takahashi A, Ichijo H, Mitochondrial fatty acid oxidation drives senescence. Sci Adv, 10(43):eado5887(2024) [pubmed]

submitter keyword: Human, LC-MS/MS

Hidenori Ichijo
contact affiliation	Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan
contact email	Ichijo@mol.f.u-tokyo.ac.jp
lab head
Shota Yamauchi
contact affiliation	Japanese Foundation for Cancer Research
contact email	yamauchi-s@umin.ac.jp
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/01/PXD036980

PRIDE project URI

• PRIDE
  1. PXD036980
     1. Label: PRIDE project
     2. Name: DNA damage response signaling to mitochondria drives senescence