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Updated: Jul 30, 2025

Studying Mitochondrial Structure and Function in Drosophila Ovaries
Published on: January 4, 2017
The mitochondrial intermembrane space protein mitofissin drives mitochondrial fission required for mitophagy
Tomoyuki Fukuda1, Kentaro Furukawa1, Tatsuro Maruyama2
1Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan.
Abstract:
Mitophagy plays an important role in mitochondrial homeostasis by selective degradation of mitochondria. During mitophagy, mitochondria should be fragmented to allow engulfment within autophagosomes, whose capacity is exceeded by the typical mitochondria mass. However, the known mitochondrial fission factors, dynamin-related proteins Dnm1 in yeasts and DNM1L/Drp1 in mammals, are dispensable for mitophagy. Here, we identify Atg44 as a mitochondrial fission factor that is essential for mitophagy in yeasts, and we therefore term Atg44 and its orthologous proteins mitofissin. In mitofissin-deficient cells, a part of the mitochondria is recognized by the mitophagy machinery as cargo but cannot be enwrapped by the autophagosome precursor, the phagophore, due to a lack of mitochondrial fission. Furthermore, we show that mitofissin directly binds to lipid membranes and brings about lipid membrane fragility to facilitate membrane fission. Taken together, we propose that mitofissin acts directly on lipid membranes to drive mitochondrial fission required for mitophagy.
Insights
Researchers discovered mitofissin (Atg44) as a crucial protein for mitochondrial fission during mitophagy. This protein enables the fragmentation of mitochondria, allowing their degradation and maintaining cellular health.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitophagy is essential for maintaining mitochondrial homeostasis through selective degradation.
- Mitochondrial fragmentation is necessary for engulfment by autophagosomes during mitophagy.
- Known mitochondrial fission factors (Dnm1/DNM1L) are not required for mitophagy.
Purpose of the Study:
- To identify novel factors involved in mitochondrial fission during mitophagy.
- To elucidate the mechanism by which mitochondria are fragmented for mitophagy.
Main Methods:
- Yeast genetics and cell biology techniques.
- Mitochondrial morphology analysis in wild-type and mutant cells.
- In vitro lipid membrane binding and fission assays.
Main Results:
- Atg44 was identified as a novel mitochondrial fission factor essential for mitophagy in yeast.
- Atg44 and its orthologs were named mitofissin.
- Mitofissin deficiency impairs mitochondrial fragmentation, hindering autophagosome engulfment.
- Mitofissin directly binds to lipid membranes and induces membrane fragility, promoting fission.
Conclusions:
- Mitofissin is a key mediator of mitochondrial fission required for mitophagy.
- Mitofissin functions by directly acting on lipid membranes to drive fission.
- This discovery provides new insights into the regulation of mitophagy and mitochondrial quality control.
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