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PXD022560-2

PXD022560 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProtein import defects induce mitophagy without membrane depolarization
DescriptionUpon 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:51:48.841.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJonas Michaelis
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-16 03:40:05ID requested
12022-09-03 03:54:24announced
22023-11-14 08:51:49announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: mitophagy, protein misfolding, mitochondrial protein import,pulsed-SILAC
Contact List
Christian Münch
contact affiliationGoethe University Frankfurt, Faculty of medicine, Institute of Biochemistry II, Münch Group
contact emailch.muench@em.uni-frankfurt.de
lab head
Jonas Michaelis
contact affiliationGoethe Universität Frankfurt am Main, Faculty of medicine, Institute of Biochemistry II, Münch Group
contact emailmichaelis@med.uni-frankfurt.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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