Format

Send to

Choose Destination
Cell Rep. 2016 Dec 13;17(11):3024-3034. doi: 10.1016/j.celrep.2016.11.049.

Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control.

Author information

1
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.
2
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
3
Department of Biology, University of Padova, Padova 35121, Italy; Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain.
4
Department of Biology, University of Padova, Padova 35121, Italy.
5
Centro Imaging Sperimentale, IRCCS Istituto Scientifico San Raffaele, Milano 20132, Italy.
6
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.
7
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec G1J 2G3, Canada.
8
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.
9
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.

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.

KEYWORDS:

MICOS; OPA1; cristae; mitochondria; proteomics

PMID:
27974214
PMCID:
PMC5186903
DOI:
10.1016/j.celrep.2016.11.049
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center