title: The INA complex facilitates assembly of the peripheral stalk of the mitochondrial F1Fo-ATP synthase.
abstract: Mitochondrial F1Fo-ATP synthase generates the bulk of cellular ATP. This molecular machine assembles from nuclear- and mitochondria-encoded subunits. Whereas chaperones for formation of the matrix-exposed hexameric F1-ATPase core domain have been identified, insight into how the nuclear-encoded F1-domain assembles with the membrane-embedded Fo-region is lacking. Here we identified the INA complex (INAC) in the inner membrane of mitochondria as an assembly factor involved in this process. Ina22 and Ina17 are INAC constituents that physically associate with the F1-module and peripheral stalk, but not with the assembled F1Fo-ATP synthase. Our analyses show that loss of Ina22 and Ina17 specifically impairs formation of the peripheral stalk that connects the catalytic F1-module to the membrane embedded Fo-domain. We conclude that INAC represents a matrix-exposed inner membrane protein complex that facilitates peripheral stalk assembly and thus promotes a key step in the biogenesis of mitochondrial F1Fo-ATP synthase.
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Lytovchenko
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Nataliia
authors.initials: N
authors.lastname: Naumenko
authors.affiliation: Department of Biochemistry and Functional Proteomics, Faculty for Biology, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Oeljeklaus
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schmidt
authors.affiliation: Institute for Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: von der Malsburg
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Deckers
authors.affiliation: Department of Biochemistry and Functional Proteomics, Faculty for Biology, University of Freiburg, Freiburg, Germany BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Warscheid
authors.affiliation: BIOSS Centre for Biological Signalling Studies, University of Freiburg, Freiburg, Germany Institute for Biochemistry and Molecular Biology, ZBMZ, University of Freiburg, Freiburg, Germany martin.van.der.laan@biochemie.uni-freiburg.de Peter.Rehling@medizin.uni-goettingen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: van der Laan
authors.affiliation: Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany Max Planck Institute for Biophysical Chemistry, Göttingen, Germany martin.van.der.laan@biochemie.uni-freiburg.de Peter.Rehling@medizin.uni-goettingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Rehling
mesh_terms: D051336:Mitochondrial Membranes / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017434:Protein Structure, Tertiary; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000591935:INA17 protein, S cerevisiae; C000591934:INA22 protein, S cerevisiae; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases
keywords: F1Fo‐ATP synthase; assembly; mitochondria; peripheral stalk