PXD065566

PXD065566 is an original dataset announced via ProteomeXchange.

Title	The PP2A-B55-alpha phosphatase is a master regulator of mitochondrial degradation and biogenesis
Description	Mitochondrial homeostasis relies on a tight balance between mitochondrial biogenesis and degradation. Although mitophagy is one of the main pathways involved in the clearance of damaged or old mitochondria, its coordination with mitochondrial biogenesis is poorly characterized.Here,by unbiased approaches including last-generation liquid chromatography coupled to mass-spectrometry and transcriptomics, we identify the protein phosphatase PP2A-B55a/PPP2R2A as a Parkin-dependent regulator of mitochondrial number. Upon mitochondrial damage, PP2A-B55a determines the amplitude of mitophagy induction and execution, by regulating both early and late mitophagy events. Few minutes after the insult, ULK1 is released from the inhibitory regulation of PP2A-B55a, whereas 2- 4 hours after mitochondrial damage PP2A-B55a promotes the nuclear translocation of TFEB, the master regulator of autophagy and lysosome genes, to support mitophagy execution. Moreover, PP2A-B55a controls a transcriptional program of mitochondrial biogenesis by regulating the stability of the Parkin substrate and PGC1-a inhibitor PARIS. Importantly, PP2A-B55a targeting rescues neurodegenerative phenotypes in a fly model of Parkinson’s disease, thus representing a potential therapeutic target in this disease.
HostingRepository	PRIDE
AnnounceDate	2025-09-24
AnnouncementXML	Submission_2025-09-24_01:42:04.324.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD065566
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sergio Lilla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-27 10:11:42	ID requested
⏵ 1	2025-09-24 01:42:04	announced

10.6019/PXD065566;

10.1126/SCIADV.ADW7376;

submitter keyword: Mitophagy, Mitochondrial biogenesis, Size Exclusion Chromatography,Phosphatase

Sergio Lilla
contact affiliation	CRUK -CRUK Scotland nstitute for Cancer Research - Switchback Rd, Bearsden, Glasgow G61 1BD - United Kingdom
contact email	s.lilla@crukscotlandinstitute.ac.uk
lab head
Sergio Lilla
contact affiliation	Proteomics
contact email	s.lilla@beatson.gla.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065566
     1. Label: PRIDE project
     2. Name: The PP2A-B55-alpha phosphatase is a master regulator of mitochondrial degradation and biogenesis