PXD030095

PXD030095 is an original dataset announced via ProteomeXchange.

Title	Multi-facetted proteomics of mitochondrial TMBIM5 deficient cell lines: Regulation of mitochondrial proteostasis by the proton gradient
Description	Mitochondria adapt to different energetic demands reshaping their proteome. Mitochondrial proteases are emerging as key regulators of these adaptive processes. Here, we use a multi-proteomic approach to demonstrate regulation of the m-AAA protease AFG3L2 by the mitochondrial proton gradient, coupling mitochondrial protein turnover to the energetic status of mitochondria. We identify TMBIM5 (previously also known as GHITM or MICS1) as a Ca2+/H+ exchanger in the mitochondrial inner membrane, which binds to and inhibits the m-AAA protease. TMBIM5 ensures cell survival and respiration, allowing Ca2+ efflux from mitochondria and limiting mitochondrial hyperpolarization. Persistent hyperpolarization, however, triggers degradation of TMBIM5 and activation of the m-AAA protease. The m-AAA protease broadly remodels the mitochondrial proteome and mediates the proteolytic breakdown of respiratory complex I to confine ROS production and oxidative damage in hyperpolarized mitochondria. TMBIM5 thus integrates mitochondrial Ca2+ signaling and the energetic status of mitochondria with protein turnover rates to reshape the mitochondrial proteome and adjust the cellular metabolism.
HostingRepository	PRIDE
AnnounceDate	2022-07-26
AnnouncementXML	Submission_2022-07-26_14:52:05.178.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hendrik Nolte
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-02 02:12:35	ID requested
⏵ 1	2022-07-26 14:52:05	announced

Dataset with its publication pending

submitter keyword: TMBIM5, AFG3L2, Mitochondria, HeLa, HEK, SILAC, Cyclohexamide, GHITM

Thomas Langer
contact affiliation	Max-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b 50931 Cologne
contact email	tlanger@age.mpg.de
lab head
Hendrik Nolte
contact affiliation	Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
contact email	h.nolte@age.mpg.de
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/2022/07/PXD030095

PRIDE project URI

• PRIDE
  1. PXD030095
     1. Label: PRIDE project
     2. Name: Multi-facetted proteomics of mitochondrial TMBIM5 deficient cell lines: Regulation of mitochondrial proteostasis by the proton gradient