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PXD034136

PXD034136 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleParkin-dependent mitophagy occurs via proteasome-dependent stepwise inwardly directed mitochondrial sub-compartment targeting to lysosomes
DescriptionPINK1/parkin-dependent mitophagy initially involves (phospho) ubiquitin-proteasome-dependent degradation of certain outer mitochondrial membrane (OMM) proteins (e.g. mitofusins) and then the recruitment of autophagy effectors to more stable ubiquitinated OMM proteins. It is widely assumed that such ubiquitinated mitochondria are ultimately degraded via wholesale mitophagy. However, we demonstrate that mitochondrial degradation occurs via step-wise delivery of separate mitochondrial sub-compartments to lysosomes. OMM and inner mitochondrial material appears to become separately isolated for autophagolysosomal degradation, not only in parkin-overexpressing HeLa cells but also in cells that express endogenous parkin (human embryonic kidney cells and neural progenitor cells) with slower mitophagy kinetics. The remaining inner mitochondrial material becomes degraded only after much prolonged membrane depolarization, involving another proteasome-sensitive step. These combined microscopy and proteomics analyses lend support to the idea that cell stress-induced parkin-dependent mitophagy is a complex regulated multi-step process with distinct sub-compartments separately targeted to autophagic degradation.
HostingRepositoryPRIDE
AnnounceDate2025-05-26
AnnouncementXMLSubmission_2025-05-25_16:37:11.347.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKatharina Zittlau
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-26 01:18:28ID requested
12025-05-25 16:37:12announced
Publication List
Lechado-Terradas A, Schepers S, Zittlau KI, Sharma K, Ok O, Fitzgerald JC, Geimer S, Westermann B, Macek B, Kahle PJ, Parkin-dependent mitophagy occurs via proteasome-dependent steps sequentially targeting separate mitochondrial sub-compartments for autophagy. Autophagy Rep, 1(1):576-602(2022) [pubmed]
10.1080/27694127.2022.2143214;
Keyword List
submitter keyword: mitochondrial outer membrane
mitophagy
parkin
proteasome
ubiquitin
Contact List
Boris Macek
contact affiliationDepartment of Biology, Quantitative Proteomics Group, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany
contact emailboris.macek@uni-tuebingen.de
lab head
Katharina Zittlau
contact affiliationUniversity of Tuebingen
contact emailKatharina.zittlau@uni-tuebingen.de
dataset submitter
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