PXD022734-1

PXD022734 is an original dataset announced via ProteomeXchange.

Title	Oxygen sensitive regulation of TFAM linking the von Hippel-Lindau cancer syndrome to impaired mitochondrial biogenesis
Description	The major consumers of oxygen in the cell are mitochondria. Here we identified an oxygen-sensitive regulation of TFAM, a key activator of mitochondrial transcription and replication. TFAM is hydroxylated by EglN3 on proline 53/56 and subsequently bound by the tumor suppressor von Hippel Lindau (pVHL). pVHL binding stabilizes TFAM by preventing mitochondrial LON proteolysis. Cells lacking wild-type VHL or in which EglN3 was inactivated genetically or by lack of oxygen have reduced mitochondria. All VHL cancer syndrome mutations tested, type 1, 2A, 2B, 2C, failed to bind hydroxylated TFAM, regardless of whether they have the ability to bind hydroxylated HIFa or not. In contrast, VHL-R200W polycythemia-mutation bound hydroxylated TFAM similar as wild-type VHL. VHL-R200W causes polycythemia with total absence of tumor development, despite increased HIFa signaling. Tumors of VHL related malignancies such as pheochromocytoma and renal carcinoma cells show low mitochondrial content, implicating that impaired mitochondrial biogenesis is linked to the malignancies of the VHL hereditary cancer syndrome.
HostingRepository	PRIDE
AnnounceDate	2022-05-25
AnnouncementXML	Submission_2022-05-25_06:23:11.246.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JIMMY RODRIGUEZ
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-25 04:24:35	ID requested
⏵ 1	2022-05-25 06:23:11	announced

Dataset with its publication pending

submitter keyword: LC-MS/MS, Oxygen regulation, TMT, Hippel-Lindau cancer syndrome, mitocondria

Susanne Schlisio
contact affiliation	Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
contact email	susanne.schlisio@ki.se
lab head
JIMMY RODRIGUEZ
contact affiliation	Division of Chemistry I, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
contact email	esneider007@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD022734
     1. Label: PRIDE project
     2. Name: Oxygen sensitive regulation of TFAM linking the von Hippel-Lindau cancer syndrome to impaired mitochondrial biogenesis