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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
PubMed

Insights

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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