title: The BH3-only Bnip3 binds to the dynamin Opa1 to promote mitochondrial fragmentation and apoptosis by distinct mechanisms.
abstract: Opa1 modulates mitochondrial fusion, cristae structure and apoptosis. The relationships between these functions and autosomal dominant optic atrophy, caused by mutations in Opa1, are poorly defined. We show that Bnip3 interacts with Opa1, leading to mitochondrial fragmentation and apoptosis. Fission is due to inhibition of Opa1-mediated fusion and is counteracted by Opa1 in an Mfn1-dependent manner. Bnip3-Opa1 interaction is necessary to trigger Opa1 complex disruption in a Bax- and/or Bak-dependent manner, ultimately leading to apoptosis. Our results uncover a direct link between Opa1 on the inner mitochondrial membrane and the apoptotic machinery on the outer membrane that modulates fusion and cristae structure by separate mechanisms. These findings might help to unravel optic atrophy aetiology as retinal ganglion cells are particularly prone to hypoxia, an inductor of Bnip3 expression.
authors.affiliation: Laboratoire Métabolisme Plasticité Mitochondries, Université Paul Sabatier and CNRS UMR5241, Université de Toulouse, Toulouse, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Landes
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Emorine
authors.forename: Delphine
authors.initials: D
authors.lastname: Courilleau
authors.forename: Manuel
authors.initials: M
authors.lastname: Rojo
authors.forename: Pascale
authors.initials: P
authors.lastname: Belenguer
authors.forename: Laetitia
authors.initials: L
authors.lastname: Arnauné-Pelloquin
mesh_terms: D017209:Apoptosis; D034281:Dynamins / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
chemical_list: C090121:BNIP3 protein, human; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D034281:Dynamins