Regulated membrane remodeling by Mic60 controls formation of mitochondrial crista junctions

Manuel Hessenberger, Ralf M Zerbes, Heike Rampelt, Séverine Kunz, Audrey H Xavier, Bettina Purfürst, Hauke Lilie, Nikolaus Pfanner, Martin van der Laan, Oliver Daumke

Research output: Journal article (peer-reviewed)Journal article

56 Citations (Scopus)

Abstract

The mitochondrial contact site and cristae organizing system (MICOS) is crucial for the formation of crista junctions and mitochondrial inner membrane architecture. MICOS contains two core components. Mic10 shows membrane-bending activity, whereas Mic60 (mitofilin) forms contact sites between inner and outer membranes. Here we report that Mic60 deforms liposomes into thin membrane tubules and thus displays membrane-shaping activity. We identify a membrane-binding site in the soluble intermembrane space-exposed part of Mic60. This membrane-binding site is formed by a predicted amphipathic helix between the conserved coiled-coil and mitofilin domains. The mitofilin domain negatively regulates the membrane-shaping activity of Mic60. Binding of Mic19 to the mitofilin domain modulates this activity. Membrane binding and shaping by the conserved Mic60-Mic19 complex is crucial for crista junction formation, mitochondrial membrane architecture and efficient respiratory activity. Mic60 thus plays a dual role by shaping inner membrane crista junctions and forming contact sites with the outer membrane.

Original languageEnglish
Article number15258
Pages (from-to)15258
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 31 May 2017
Externally publishedYes

Keywords

  • Amino Acid Sequence
  • Cell Membrane/metabolism
  • Liposomes
  • Mitochondrial Membranes/metabolism
  • Mitochondrial Proteins/chemistry
  • Protein Binding
  • Saccharomyces cerevisiae/metabolism
  • Saccharomyces cerevisiae Proteins/metabolism
  • Sequence Homology, Amino Acid

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