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MFF budding from mitochondria regulates melanosome size and maturation
Ana Paula Magalhães Rebelo1,2, Aurora Maracani3,4, Samuele Greco5
1Department of Biology, University of Padova, Padua, Italy. amagalha@uni-koeln.de.
Nature Communications
|March 15, 2026
Summary
Mitochondrial fission factor protein (MFF) drives melanosome fission, a key step in melanin production and organelle maturation. This process involves actin regulation, revealing MFF
Area of Science:
- Cell Biology
- Organelle Biology
- Melanin Biology
Background:
- Melanosomes are organelles responsible for melanin production and accumulation.
- Melanosome maturation involves protein export, recycling, and fission, with unknown mechanisms.
- Mitochondria interact with melanosomes during maturation.
Purpose of the Study:
- To investigate the role of mitochondrial fission factor protein (MFF) in melanosome fission and maturation.
- To elucidate the molecular mechanisms underlying MFF-mediated melanosome fission.
Main Methods:
- Downregulation of MFF and dynamin-related protein 1 (DRP1) using genetic silencing.
- Microscopy to observe melanosome morphology and MFF localization.
- Analysis of protein interactions with ARP2/3 complex regulators.
- Assessment of F-actin dynamics and melanosome size.
Main Results:
- MFF is localized at melanosome fission sites and is essential for melanosome fission.
- MFF downregulation leads to enlarged melanosomes, increased melanin accumulation, and enhanced lysosomal catabolism.
- MFF interacts with ARP2/3 complex regulators, promoting actin nucleation at fission sites.
- MFF regulates actin-dependent melanosome fission.
Conclusions:
- MFF plays a critical role in melanosome fission and maturation, independent of DRP1.
- MFF utilizes the ARP2/3 complex and actin filaments for melanosome fission.
- MFF has an extramitochondrial function in regulating melanosome homeostasis.
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