PXD056318

PXD056318 is an original dataset announced via ProteomeXchange.

Title	Cycloheximide time course in WT and AFG3L2 knockout HeLa cells
Description	Mitochondria are metabolically rewired in hypoxia when cells switch to glycolytic growth. In addition to the well-established role of transcriptional and translational programs, there is increasing evidence that post-translational mechanisms contribute to the rapid adaptation of the mitochondrial proteome to hypoxia. Here, we have used a proteomic survey to define how the m-AAA protease AFG3L2, a proteolytic complex in the inner mitochondrial membrane, regulates mitochondrial proteostasis. Our experiments identify a broad spectrum of mitochondrial substrate proteins and show that AFG3L2 is activated in hypoxia along an HIF1-mTORC1 signaling axis. AFG3L2-mediated proteolysis restricts mitochondrial biogenesis and gene expression by degrading proteins, which are involved in mitochondrial protein import, mitochondrial transcription, mRNA processing, modification and stability, and RNA granule formation. Our experiments highlight the important contribution of proteolytic rewiring of the mitochondrial proteome for the adaptation to low oxygen tension and shed new light on the pathophysiology of several neurodegenerative disorders associated with mutations in AFG3L2. This dataset is part of a collection of different datasets of the above-mentioned project. Here we studied the protein degradation in HeLa cells in conditions where translation is blocked using cycloheximide. Please note that there is a file describing (0069_SampleNames) that indicates the raw file - sample matching table but also indicates if a sample has been excluded because it did not pass the quality control standards (for example number of proteins quantified). Please note that also SPG7KO and AFG3L2 and SPG7 double KO were measured in this project, but are not part of the paper.
HostingRepository	PRIDE
AnnounceDate	2026-01-06
AnnouncementXML	Submission_2026-01-06_10:34:51.069.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: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-27 02:13:45	ID requested
⏵ 1	2026-01-06 10:34:51	announced

Dataset with its publication pending

submitter keyword: Cycloheximide, HeLa, mitochondria, AFG3L2

Thomas Langer
contact affiliation	Max-Planck Institut for Biology of Ageing Department Langer - 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/2026/01/PXD056318

PRIDE project URI

• PRIDE
  1. PXD056318
     1. Label: PRIDE project
     2. Name: Cycloheximide time course in WT and AFG3L2 knockout HeLa cells