PXD034136

PXD034136 is an original dataset announced via ProteomeXchange.

Title	Parkin-dependent mitophagy occurs via proteasome-dependent stepwise inwardly directed mitochondrial sub-compartment targeting to lysosomes
Description	PINK1/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.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_16:37:11.347.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katharina Zittlau
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-26 01:18:28	ID requested
⏵ 1	2025-05-25 16:37:12	announced

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;

submitter keyword: mitochondrial outer membrane

mitophagy

parkin

proteasome

ubiquitin

Boris Macek
contact affiliation	Department of Biology, Quantitative Proteomics Group, Interfaculty Institute of Cell Biology, University of Tübingen, Tübingen, Germany
contact email	boris.macek@uni-tuebingen.de
lab head
Katharina Zittlau
contact affiliation	University of Tuebingen
contact email	Katharina.zittlau@uni-tuebingen.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/2025/05/PXD034136

PRIDE project URI

• PRIDE
  1. PXD034136
     1. Label: PRIDE project
     2. Name: Parkin-dependent mitophagy occurs via proteasome-dependent stepwise inwardly directed mitochondrial sub-compartment targeting to lysosomes