PXD062948-1

PXD062948 is an original dataset announced via ProteomeXchange.

Title	Regulation of mitophagy by Fis1 and Fascin1-organized actin
Description	Mitophagy, the autophagic degradation of mitochondria, plays a central role in controlling the quality and quantity of mitochondria, thereby ensuring cellular health. The mitochondrial outer membrane protein Fis1 is important for several types of mitophagy, but its mechanism of action remains unclear. F-actin is recruited to autophagic cargo and is important for autophagic progression, but the mechanism for its recruitment is poorly understood. To address the molecular function of Fis1, we performed affinity purification of Fis1 and mass spectrometry and identified the actin-bundling protein Fascin1 as a physical interactor. We demonstrate that Fis1 is required for recruitment of Fascin1 as well as F-actin to mitochondria under stress conditions, including mitochondrial depolarization and iron chelation. Iron chelation also triggers mitophagy that is independent of the Parkinson's associated gene Parkin, and we show that Fis1 enables recruitment of Fascin1-organized F-actin to facilitate proper morphogenesis of autophagosomes and the ensuing mitochondrial degradation. In contrast, although Parkin-mediated mitophagy also relies on Fis1, it is unaffected by loss of Fascin1 or F-actin recruitment. These findings indicate that Fis1 has distinct modes of action in mitophagy, depending on the triggering cellular stress. They establish Fis1 as a key driver of Fascin1 and F-actin recruitment to mitochondria, events that are critical for autophagosome morphogenesis during iron-chelation-induced mitophagy.
HostingRepository	PRIDE
AnnounceDate	2026-07-07
AnnouncementXML	Submission_2026-07-07_10:13:22.089.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ting-Yu Wang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-14 14:02:15	ID requested
⏵ 1	2026-07-07 10:13:22	announced

10.1016/j.cub.2026.01.062;

Nakajima S, Wang TY, Chou TF, Chakrabarty Y, Chan DC, Regulation of mitophagy by Fis1 and Fascin1-organized actin. Curr Biol, 36(5):1205-1219.e8(2026) [pubmed]

submitter keyword: mitophagy, Fascin1, Fis1,mitochondria, actin filaments

Tsui-Fen Chou
contact affiliation	Proteome Exploration Laboratory, Beckman Institute, California Institute of Technology, Pasadena,CA 91125, USA.
contact email	tfchou@caltech.edu
lab head
Ting-Yu Wang
contact affiliation	Caltech
contact email	tywang@caltech.edu
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/2026/07/PXD062948

PRIDE project URI

• PRIDE
  1. PXD062948
     1. Label: PRIDE project
     2. Name: Regulation of mitophagy by Fis1 and Fascin1-organized actin