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

  • Christina Glytsou
  • , Enrique Calvo
  • , Sara Cogliati
  • , Arpit Mehrotra
  • , Irene Anastasia
  • , Giovanni Rigoni
  • , Andrea Raimondi
  • , Norihito Shintani
  • , Marta Loureiro
  • , Jesùs Vazquez
  • , Luca Pellegrini
  • , Jose Antonio Enriquez
  • , Luca Scorrano
  • , Maria Eugenia Soriano

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
Pages (from-to)3024-3034
Number of pages11
JournalCell Reports
Volume17
Issue number11
DOIs
StatePublished - Dec 13 2016
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

Keywords

  • MICOS
  • OPA1
  • cristae
  • mitochondria
  • proteomics

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