Related Experiment Video

Updated: Oct 7, 2025

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.3K

The SUMO protease SENP3 regulates mitochondrial autophagy mediated by Fis1

Emily Waters1, Kevin A Wilkinson2, Amy L Harding3

  • 1School of Biosciences, University of Sheffield, Sheffield, UK.

EMBO Reports
|January 7, 2022
PubMed

Insights

Cells eliminate damaged mitochondria via mitophagy, a process crucial for health. This study reveals that the SUMO protease SENP3 stabilizes mitochondrial fission protein Fis1, promoting mitophagy under stress.

Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Protein Post-Translational Modifications

Background:

  • Mitochondria face constant stress from reactive species.
  • Mitophagy is a quality control mechanism for removing dysfunctional mitochondria.
  • The molecular mechanisms of stress-induced mitophagy remain incompletely understood.

Purpose of the Study:

  • To investigate the molecular basis of stress-induced mitophagy using deferiprone (DFP) as a model stressor.
  • To elucidate the role of mitochondrial fission 1 protein (Fis1) and its SUMOylation status in this process.

Main Methods:

  • Utilized deferiprone (DFP) to induce mitochondrial stress.
  • Investigated the role of Fis1, SUMOylation, and the SUMO protease SENP3.
  • Employed genetic manipulation, including K149R mutation and SENP3 depletion, to assess functional impacts.

Main Results:

  • Fis1 is essential for DFP-induced mitophagy.
  • Fis1 SUMOylation at K149 is critical for its mitochondrial localization.
  • DFP stabilizes SENP3 by downregulating the E3 ubiquitin ligase CHIP.
  • SENP3-mediated deSUMOylation of Fis1 is required for DFP-induced mitophagy.
  • Preventing Fis1 SUMOylation enhances its mitochondrial localization and restores mitophagy in SENP3-depleted cells.

Conclusions:

  • A model is proposed where SENP3-mediated deSUMOylation of Fis1 facilitates its mitochondrial localization, thereby driving stress-induced mitophagy.
  • This highlights a novel regulatory pathway controlling mitochondrial quality control under stress conditions.
Keywords:
Fis1SENP3SUMOmitophagyorganellar stress

More Related Videos

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs08:15

Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs

Published on: August 15, 2025

420
Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima09:13

Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima

Published on: August 12, 2018

15.1K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
7.3K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.1K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.8K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.6K
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial...
2.7K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.2K