PXD022560-1

PXD022560 is an original dataset announced via ProteomeXchange.

Title	Protein import defects induce mitophagy without membrane depolarization
Description	Upon mitochondrial dysfunction, mitophagy has been described to be activated by a breakdown of membrane potential leading to PINK1 accumulation on the outer membrane and engulfment of mitochondria for degradation. However, recent findings have indicated that mitophagy may also be triggered in the absence of membrane potential alterations. Here, we report mechanistic details on how inhibition of protein import induces mitophagy independent of mitochondrial membrane depolarization. Carrying out a genome-wide CRISPR/Cas9 screen for regulators of mitophagy, we found that the pre-sequence translocase-associated motor complex PAM controls mitophagy induction. Loss of PAM caused defects in protein import and was sufficient to induce mitophagy without depolarization. Quantitative interaction and aggregation proteomics revealed that PAM was highly sensitive to proteostasis perturbation; upon misfolding conditions, PAM dissociated from the import machinery, sequestered into the insoluble fraction and caused mitophagy despite an intact membrane potential. Our findings extend the current mitophagy model and provide mechanistic insight into how proteostasis perturbation leads to mitophagy induction. They reveal the PAM complex as key folding sensor integrating proteostasis, import and mitophagy.
HostingRepository	PRIDE
AnnounceDate	2022-09-03
AnnouncementXML	Submission_2022-09-03_03:54:23.888.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonas Michaelis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-11-16 03:40:05	ID requested
⏵ 1	2022-09-03 03:54:24	announced
2	2023-11-14 08:51:49	announced	2023-11-14: Updated project metadata.

10.1038/S41467-022-32564-X;

submitter keyword: pulsed-SILAC, mitochondrial protein import, protein misfolding, mitophagy

Christian Münch
contact affiliation	Goethe University Frankfurt, Faculty of medicine, Institute of Biochemistry II, Münch Group
contact email	ch.muench@em.uni-frankfurt.de
lab head
Jonas Michaelis
contact affiliation	Goethe Universität Frankfurt am Main, Faculty of medicine, Institute of Biochemistry II, Münch Group
contact email	michaelis@med.uni-frankfurt.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/2022/09/PXD022560

PRIDE project URI

• PRIDE
  1. PXD022560
     1. Label: PRIDE project
     2. Name: Protein import defects induce mitophagy without membrane depolarization