Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis

Tiziana Daniele, Ilse Hurbain, Riccardo Vago, Giorgio Casari, Graça Raposo, Carlo Tacchetti, Maria Vittoria Schiaffino

Research output: Contribution to journalArticle

Abstract

Background To efficiently supply ATP to sites of high-energy demand and finely regulate calcium signaling, mitochondria adapt their metabolism, shape, and distribution within the cells, including relative positioning with respect to other organelles. However, physical contacts between mitochondria and the secretory/endocytic pathway have been demonstrated so far only with the ER, through structural and functional interorganellar connections. Results Here we show by electron tomography that mitochondria physically contact melanosomes, specialized lysosome-related organelles of pigment cells, through fibrillar bridges resembling the protein tethers linking mitochondria and the ER. Mitofusin (Mfn) 2, which bridges ER to mitochondria, specifically localizes also to melanosome-mitochondrion contacts, and its knockdown significantly reduces the interorganellar connections. Contacts are associated to the melanogenesis process, as indicated by the fact that they are reduced in a model of aberrant melanogenesis whereas they are enhanced both where melanosome biogenesis takes place in the perinuclear area and when it is actively stimulated by OA1, a G protein-coupled receptor implicated in ocular albinism and organellogenesis. Consistently, Mfn2 knockdown prevents melanogenesis activation by OA1, and the pharmacological inhibition of mitochondrial ATP synthesis severely reduces contact formation and impairs melanosome biogenesis, by affecting in particular the developing organelles showing the highest frequency of contacts. Conclusions Altogether, our findings reveal the presence of an unprecedented physical and functional connection between mitochondria and the secretory/endocytic pathway that goes beyond the ER-mitochondria linkage and is spatially and timely associated to secretory organelle biogenesis.

Original languageEnglish
Pages (from-to)393-403
Number of pages11
JournalCurrent Biology
Volume24
Issue number4
DOIs
Publication statusPublished - Feb 17 2014

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Melanosomes
Mitochondria
Organelle Biogenesis
organelles
mitochondria
melanogenesis
Organelles
Secretory Pathway
Ocular Albinism
Adenosine Triphosphate
Electron Microscope Tomography
Calcium Signaling
biogenesis
tomography
lysosomes
G-Protein-Coupled Receptors
Lysosomes
albino
Metabolism
Pigments

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mitochondria and melanosomes establish physical contacts modulated by Mfn2 and involved in organelle biogenesis. / Daniele, Tiziana; Hurbain, Ilse; Vago, Riccardo; Casari, Giorgio; Raposo, Graça; Tacchetti, Carlo; Schiaffino, Maria Vittoria.

In: Current Biology, Vol. 24, No. 4, 17.02.2014, p. 393-403.

Research output: Contribution to journalArticle

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