PXD063602-1

PXD063602 is an original dataset announced via ProteomeXchange.

Title	AIFM1 KO and AIFM1del mutant HEK cell proteomics
Description	Mitochondrial proteases regulate the dynamic properties of the organelle morphology and ensure functional plasticity at the cellular level. The metalloprotease OMA1 mediates constitutive and stress-inducible processing of its substrates in mitochondria, but the number of functionally characterized substrates remains limited. Using multiproteomic and biochemical approaches, we show that the membrane-anchored inner membrane space (IMS) protein AIFM1 serves as a mitochondrial stress-responsive substrate of OMA1. We define that OMA1 cleaves AIFM1 in the IMS under stress conditions, which is a kinetically slower reaction than that of the conventional substrate, the dynamin-like GTPase OPA1. Membrane dislocation of cleaved AIFM1 in mitochondria reduces its binding to subunits of the oxidative phosphorylation machinery. This leads to a decrease in the respiratory activity and ultimately impairs cell growth. Mechanistically, we show that AIFM1 broadly safeguards the mitochondrial proteome at steady state by participating in the protein import, in particular respiratory complex I subunits, via the Tim23 complex. These results reveal an unrecognized role for OMA1 in integrating mitochondrial stress sensing and cellular energetics by altering the topology of AIFM1. The internal identifier was: m4m1hgAENC The repository contains AIFM1 wildtype and KO TREx cells (samples 1-8), which were not used in the associated publication. The file names contain pp for +/+ and mm for -/-. File names 09-12 (file names: R98ENLYFG) correspond to TCS. The file names 13-16 (M1_R98del) correspond to TCS/TEV. Raw file Sample Name 01_AIFM1_KO_pp_fyxK.raw Flp-In-T REx-293-mock#1 02_AIFM1_KO_pp_wxP9.raw Flp-In-T REx-293-mock#2 03_AIFM1_KO_pp_Djpr.raw Flp-In-T REx-293-mock#3 04_AIFM1_KO_pp_txOk.raw Flp-In-T REx-293-mock#4 05_AIFM1_KO_mm_moaT.raw Flp-In-T REx-293 AIFM1 KO-mock#1 06_AIFM1_KO_mm_W5lK.raw Flp-In-T REx-293 AIFM1 KO-mock#2 07_AIFM1_KO_mm_XIc0.raw Flp-In-T REx-293 AIFM1 KO-mock#3 08_AIFM1_KO_mm_pdxt.raw Flp-In-T REx-293 AIFM1 KO-mock#4 09_AIFM1_C_MycAIFM1_R98ENLYFG_I2x8.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS#1 10_AIFM1_C_MycAIFM1_R98ENLYFG_Hzqq.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS#2 11_AIFM1_C_MycAIFM1_R98ENLYFG_4P4M.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS#3 12_AIFM1_C_MycAIFM1_R98ENLYFG_MktX.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS#4 13_AIFM1_C_MycAIFM1_M1_R98del_7NiF.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS/TEV#1 14_AIFM1_C_MycAIFM1_M1_R98del_yf68.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS/TEV#2 15_AIFM1_C_MycAIFM1_M1_R98del_hmKM.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS/TEV#3 16_AIFM1_C_MycAIFM1_M1_R98del_qXgO.raw Flp-In-T REx-293 AIFM1 KO-AIFM1TCS/TEV#4
HostingRepository	PRIDE
AnnounceDate	2026-01-31
AnnouncementXML	Submission_2026-01-31_00:33:40.499.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	2025-05-05 05:39:47	ID requested
⏵ 1	2026-01-31 00:33:40	announced

Dataset with its publication pending

submitter keyword: AIFM1, Mitochondrion,HEK

Thomas Langer
contact affiliation	Max-Planck-Institute for Biology of Ageing Department of Mitochondrial Proteostasis Joseph-Stelzmann-Str. 9b 50931 Cologne Germany
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/PXD063602

PRIDE project URI

• PRIDE
  1. PXD063602
     1. Label: PRIDE project
     2. Name: AIFM1 KO and AIFM1del mutant HEK cell proteomics