Both inner and outer mitofissins are required for mitochondrial fission during mitophagy
Selective degradation of damaged or excess mitochondria to maintain mitochondrial homeostasis is termed mitophagy.
In addition to previously identified inner mitochondrial space resident mitofissin/Atg44, the authors in this study identified Mfi2, a mitochondrial outer membrane-resident mitofissin, required for mitophagy.
They demonstrate that Mfi2 associates with the mitochondrial membrane in a cardiolipin-dependent manner.
Overexpression of an N-terminal Atg44-like region of Mfi2 induces mitochondrial fragmentation and partially restores mitophagy in atg44 deleted cells.
The authors also show that Mfi2 and Dnm1 independently facilitate mitochondrial fission during mitophagy.
Mfi2 and the dynamin-related protein Dnm1 promote mitophagy-associated mitochondrial fission from outside the mitochondria, together with the inner mitofissin Atg44.
https://link.springer.com/article/10.1038/s44319-025-00689-x
