title: The novel component Kgd4 recruits the E3 subunit to the mitochondrial α-ketoglutarate dehydrogenase.
abstract: The mitochondrial citric acid cycle is a central hub of cellular metabolism, providing intermediates for biosynthetic pathways and channeling electrons to the respiratory chain complexes. In this study, we elucidated the composition and organization of the multienzyme complex α-ketoglutarate dehydrogenase (α-KGDH). In addition to the three classical E1-E3 subunits, we identified a novel component, Kgd4 (Ymr31/MRPS36), which was previously assigned to be a subunit of the mitochondrial ribosome. Biochemical analyses demonstrate that this protein plays an evolutionarily conserved role in the organization of mitochondrial α-KGDH complexes of fungi and animals. By binding to both the E1-E2 core and the E3 subunit, Kgd4 acts as a molecular adaptor that is necessary to a form a stable α-KGDH enzyme complex. Our work thus reveals a novel subunit of a key citric acid-cycle enzyme and shows how this large complex is organized.
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Manfred
authors.initials: M
authors.lastname: Heublein
authors.affiliation: Cancer Centrum Karolinska, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Burguillos
authors.affiliation: Institute for Biochemistry and Molecular Biology and BIOSS (Centre for Biological Signaling Studies), University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: F Nora
authors.initials: FN
authors.lastname: Vögtle
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Teixeira
authors.affiliation: Zentrallabor für Proteinanalytik, Adolf-Butenandt Institut, LMU München, D-80336 München, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.affiliation: Institute for Biochemistry and Molecular Biology and BIOSS (Centre for Biological Signaling Studies), University of Freiburg, D-79104 Freiburg, Germany.
authors.forename: Chris
authors.initials: C
authors.lastname: Meisinger
authors.affiliation: Center for Biomembrane Research, Department of Biochemistry and Biophysics, Stockholm University, SE-106 91 Stockholm, Sweden martin.ott@dbb.su.se.
authors.forename: Martin
authors.initials: M
authors.lastname: Ott
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017124:Conserved Sequence; D019143:Evolution, Molecular; D055785:Gene Knockdown Techniques; D007655:Ketoglutarate Dehydrogenase Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D024101:Mitochondrial Proteins; D021122:Protein Subunits; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; C060587:YMR31 protein, S cerevisiae; D007655:Ketoglutarate Dehydrogenase Complex