Proteomics

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Delivery of MFF through mitochondria-derived vesicles regulates melanosome maturation


ABSTRACT: Melanosomes are lysosome-associated organelles that produce and accumulate melanin. Their biogenesis begins with the trafficking of melanogenic proteins from the endo-lysosomal system into non-pigmented vacuoles derived from endosomes. Subsequently, melanosome maturation proceeds with the export and recycling of non-required cargo, through tubular carriers and vesicular fission derived from melanosome membranes. Although constriction events have been observed at melanosome membranes, the mechanisms underlying their fission remain unclear. We found that MFF is delivered to melanosomes by mitochondria-derived vesicles (MDVs) and that it is located at melanosome membrane fission sites. Downregulation of MFF leads to an increase in the size of early melanosomes, accumulation of intracellular melanin, and increased melanosome lumen catabolism. In melanocytes, MFF interactome highlighted its interplay with a complex network of cytoskeletal factors. Inhibition of actin nucleation is indeed sufficient to restore the effects on melanosome size. Our data show for the first time that MDVs-mediated MFF trafficking to melanosomes is necessary for their membrane remodeling and fission, promoting the transition from early to mature stage melanosomes.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Nerve Cord, Cell Culture

SUBMITTER: Francescopaolo Iavarone  

LAB HEAD: Marta Giacomello

PROVIDER: PXD051372 | Pride | 2026-05-25

REPOSITORIES: Pride

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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 M  ...[more]

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