PXD056376

PXD056376 is an original dataset announced via ProteomeXchange.

Title	Mitochondrial VHL rewires cell metabolism in hypoxia
Description	Under normoxia, von Hippel-Lindau (VHL) protein targets the oxygen-induced, hydroxylated form of hypoxia-inducible factors for degradation to orchestrate mammalian oxygen sensing. However, whether VHL plays non-canonical roles in hypoxia, when protein hydroxylation is attenuated, remains elusive. Here we show that most cytosolic VHL is degraded under chronic hypoxia, with the remaining VHL pool primarily translocating to the mitochondria. Mitochondrial VHL binds and inhibits MCCC2, an essential subunit of leucine catabolic machinery. Accumulated leucine allosterically activates glutamate dehydrogenase to promote glutaminolysis, generating sufficient lipids and nucleotides to support hypoxic cell growth. Furthermore, SRC-mediated VHL phosphorylation and PRMT5-mediated MCCC2 methylation synergistically regulate the VHL-MCCC2 interaction and concomitant metabolic changes, which are recapitulated in animal models of pathological hypoxia and functionally associated with VHL mutation subtypes in cancer.
HostingRepository	PRIDE
AnnounceDate	2025-08-26
AnnouncementXML	Submission_2025-08-26_07:45:44.008.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	李 国邦
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-30 02:49:27	ID requested
⏵ 1	2025-08-26 07:45:44	announced

Dataset with its publication pending

submitter keyword: Mitochondrial VHL hypoxia metabolism

LI GUOBANG
contact affiliation	Guangdong Provincial People's Hospital
contact email	990336853@qq.com
lab head
李 国邦
contact affiliation	Guangdong Provincial People's Hospital
contact email	990336853@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056376
     1. Label: PRIDE project
     2. Name: Mitochondrial VHL rewires cell metabolism in hypoxia