title: Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control.
abstract: The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis. Whether and how they physically and functionally interact is unclear. Here, we provide evidence that OPA1 is epistatic to MICOS in the regulation of cristae shape. Proteomic analysis identifies multiple MICOS components in native OPA1-containing high molecular weight complexes disrupted during cristae remodeling. MIC60, a core MICOS protein, physically interacts with OPA1, and together, they control cristae junction number and stability, OPA1 being epistatic to MIC60. OPA1 defines cristae width and junction diameter independently of MIC60. Our combination of proteomics, biochemistry, genetics, and electron tomography provides a unifying model for mammalian cristae biogenesis by OPA1 and MICOS.
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy; IRCCS Fondazione Santa Lucia, Rome 00179, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova 35129, Italy.
authors.forename: Christina
authors.initials: C
authors.lastname: Glytsou
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Calvo
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Cogliati
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy.
authors.forename: Arpit
authors.initials: A
authors.lastname: Mehrotra
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Anastasia
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rigoni
authors.affiliation: Centro Imaging Sperimentale, IRCCS Istituto Scientifico San Raffaele, Milano 20132, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raimondi
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova 35129, Italy; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Shintani
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Loureiro
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Jesùs
authors.initials: J
authors.lastname: Vazquez
authors.affiliation: Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec G1J 2G3, Canada.
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.affiliation: Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Enriquez
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova 35129, Italy. Electronic address: luca.scorrano@unipd.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Scorrano
authors.affiliation: Department of Biology, University of Padova, Padova 35121, Italy; Dulbecco-Telethon Institute, Venetian Institute of Molecular Medicine, Padova 35129, Italy. Electronic address: mariaeugenia.soriano@unipd.it.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Soriano
mesh_terms: D017209:Apoptosis / Q000235:genetics; D004843:Epistasis, Genetic; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D008928:Mitochondria / Q000235:genetics* / Q000473:pathology; D029241:Optic Atrophy, Autosomal Dominant / Q000235:genetics* / Q000473:pathology; D020543:Proteome / Q000235:genetics; D040901:Proteomics
chemical_list: D020543:Proteome; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: MICOS; OPA1; cristae; mitochondria; proteomics