The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1

Abstract: Mitochondria are unavoidably subject to organellar stress resulting from exposure to a range of reactive molecular species. Consequently, cells operate a poorly understood quality control programme of mitophagy to facilitate elimination of dysfunctional mitochondria. Here, we used a model stressor, deferiprone (DFP), to investigate the molecular basis for stress‐induced mitophagy. We show that mitochondrial fission 1 protein (Fis1) is required for DFP‐induced mitophagy and that Fis1 is SUMOylated at K149, an amino acid residue critical for Fis1 mitochondrial localization. We find that DFP treatment leads to the stabilization of the SUMO protease SENP3, which is mediated by downregulation of the E3 ubiquitin (Ub) ligase CHIP. SENP3 is responsible for Fis1 deSUMOylation and depletion of SENP3 abolishes DFP‐induced mitophagy. Furthermore, preventing Fis1 SUMOylation by conservative K149R mutation enhances Fis1 mitochondrial localization. Critically, expressing a Fis1 K149R mutant restores DFP‐induced mitophagy in SENP3‐depleted cells. Thus, we propose a model in which SENP3‐mediated deSUMOylation facilitates Fis1 mitochondrial localization to underpin stress‐induced mitophagy.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1 ; day:07 ; month:01 ; year:2022 ; extent:16
EMBO reports / European Molecular Biology Organization ; (07.01.2022) (gesamt 16)

Urheber
Waters, Emily
Wilkinson, Kevin A.
Harding, Amy L.
Carmichael, Ruth E.
Robinson, Darren
Colley, Helen E.
Guo, Chun

DOI
10.15252/embr.201948754
URN
urn:nbn:de:101:1-2022010714150563051783
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:30 MESZ

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Beteiligte

  • Waters, Emily
  • Wilkinson, Kevin A.
  • Harding, Amy L.
  • Carmichael, Ruth E.
  • Robinson, Darren
  • Colley, Helen E.
  • Guo, Chun

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