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 journalArticle

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 languageEnglish
Pages (from-to)3024 - 3034
Number of pages11
JournalCell Reports
Volume17
Issue number11
DOIs
Publication statusPublished - Dec 13 2016

Keywords

  • cristae
  • MICOS
  • mitochondria
  • OPA1
  • proteomics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Glytsou, C., Calvo, E., Cogliati, S., Mehrotra, A., Anastasia, I., Rigoni, G., Raimondi, A., Shintani, N., Loureiro, M., Vazquez, J., Pellegrini, L., Enriquez, J. A., Scorrano, L., & Soriano, M. E. (2016). Optic Atrophy 1 Is Epistatic to the Core MICOS Component MIC60 in Mitochondrial Cristae Shape Control. Cell Reports, 17(11), 3024 - 3034. https://doi.org/10.1016/j.celrep.2016.11.049