MFF budding from mitochondria regulates melanosome size and maturation
Melanosomes are lysosome-related organelles that produce and accumulate melanin. Their maturation is regulated through interactions with mitochondria and involves the export and recycling of proteins via tubular transport and fission events whose mechanisms are unknown. Here, we demonstrate that the mitochondrial fission factor protein (MFF) is involved in melanosome fission. MFF is trafficked between mitochondria and melanosomes and locates at melanosome fission events. Upon downregulation of MFF, but not of dynamin-related protein 1 (DRP1), melanosomes enlarge, intracellular melanin accumulates, and melanosomal lumenal catabolism increases, indicating that MFF-dependent melanosome fission is required for their maturation. We show that MFF interacts with regulators of the ARP2/3 complex, which drives F-actin nucleation. Actin filaments accumulate between melanosomes at MFF-enriched membrane constriction sites, and silencing of ARP2/3 subunits mimics the increase in melanosome size. MFF regulates actin-dependent fission of melanosomes via the ARP2/3 complex, indicating an extramitochondrial function for MFF in the regulation of melanosome homeostasis.
Authors
- Samuele Greco (ORCID: https://orcid.org/0000-0003-3435-2656)
- Sara Schiavon
- Aurora Maracani
- Christian Frezza (ORCID: https://orcid.org/0000-0002-3293-7397)
- Marta Giacomello (ORCID: https://orcid.org/0000-0002-0290-6602)
- Federica Dal Bello (ORCID: https://orcid.org/0000-0002-9323-955X)
- Philip S. Goff (ORCID: https://orcid.org/0000-0003-4371-5527)
- Alberto Pallavicini (ORCID: https://orcid.org/0000-0001-7174-4603)
- Luca Scorrano (ORCID: https://orcid.org/0000-0002-8515-8928)
- Elena V. Sviderskaya
- Ana Paula Magalhães Rebelo (ORCID: https://orcid.org/0000-0001-8811-4181)
- Lucia Santorelli (ORCID: https://orcid.org/0000-0002-1883-712X)
- Tomáš Knedlík (ORCID: https://orcid.org/0000-0001-7162-6631)
- Paolo Grumati (ORCID: https://orcid.org/0000-0002-9942-9389)
- Marco Gerdol
Institutions
- University of Padua (IT)
- University of Trieste (IT)
- St George's, University of London (GB)
- Veneto Institute of Molecular Medicine (IT)
- Federico II University Hospital (IT)
- Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases (DE)
- Telethon Institute Of Genetics And Medicine (IT)
- City St George's, University of London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-14
- DOI
- https://doi.org/10.1038/s41467-026-70572-3
- Primary Topic
- melanin and skin pigmentation
- Type
- article
- Field-Weighted Citation Impact
- 0.00