Related Experiment Video

Updated: Feb 23, 2026

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome
07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

6.3K

Mitochondrial fission facilitates the selective mitophagy of protein aggregates

Jonathon L Burman1, Sarah Pickles1, Chunxin Wang1

  • 1Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

The Journal of Cell Biology
|September 13, 2017
PubMed

Insights

Mitochondrial fission does not promote mitophagy; instead, it protects healthy mitochondria from being cleared during proteotoxicity. Loss of fission enhances Parkin recruitment and mitophagy rates.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Autophagy

Background:

  • Protein aggregation in mitochondria triggers stress responses like the mitochondrial unfolded protein response and PINK1-Parkin mitophagy.
  • Autophagy is crucial for clearing protein aggregates within mitochondria, with mitochondrial fission's role being investigated.

Purpose of the Study:

  • To investigate the role of mitochondrial fission in the process of mitophagy.
  • To understand how autophagy eliminates protein aggregates from within mitochondria.

Main Methods:

  • Inducing mitochondrial proteotoxicity using actinonin.
  • Analyzing the recruitment of PINK1 and Parkin to mitochondria.
  • Observing the colocalization of Parkin with ubiquitin, optineurin, and LC3 on damaged mitochondria.
  • Inhibiting Drp1-mediated mitochondrial fission and assessing its impact on aggregate clearance and mitophagy.

Main Results:

  • PINK1 recruits Parkin to mitochondrial subdomains containing misfolded mutant ornithine transcarbamylase (ΔOTC) aggregates.
  • Parkin, ubiquitin, optineurin, and LC3 colocalize on polarized mitochondria with protein aggregates.
  • Inhibiting Drp1-mediated fission reduced subdomain segregation of ΔOTC but did not decrease clearance rates.
  • Loss of Drp1 enhanced Parkin recruitment to fused mitochondrial networks, increased mitophagy rates, and decreased selectivity for ΔOTC.

Conclusions:

  • Mitochondrial fission does not promote mitophagy; rather, it segregates damaged components.
  • Fission protects healthy mitochondrial domains from elimination by excessive PINK1-Parkin activity.
  • The study proposes a revised model where fission limits mitophagy, preventing the clearance of healthy mitochondria.

More Related Videos

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy09:29

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

Published on: May 4, 2016

7.6K
Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes11:59

Author Spotlight: Detection of Mitophagy in Caenorhabditis elegans and Mammalian Cells Using Organelle-Specific Dyes

Published on: May 19, 2023

3.2K

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,...
13.5K
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...
5.8K
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,...
6.0K
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...
3.8K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.4K
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
4.9K