title: Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex.
abstract: We have analyzed the distribution of mitochondrial contact site and cristae organizing system (MICOS) complex proteins and mitochondrial intermembrane space bridging complex (MIB) proteins over (sub)complexes and over species. The MICOS proteins are associated with the formation and maintenance of mitochondrial cristae. Indeed, the presence of MICOS genes in genomes correlates well with the presence of cristae: all cristae containing species have at least one MICOS gene and cristae-less species have none. Mic10 is the most widespread MICOS gene, while Mic60 appears be the oldest one, as it originates in the ancestors of mitochondria, the proteobacteria. In proteobacteria the gene occurs in clusters with genes involved in heme synthesis while the protein has been observed in intracellular membranes of the alphaproteobacterium Rhodobacter sphaeroides. In contrast, Mic23 and Mic27 appear to be the youngest MICOS proteins, as they only occur in opisthokonts. The remaining MICOS proteins, Mic10, Mic19, Mic25 and Mic12, the latter we show to be orthologous to human C19orf70/QIL1, trace back to the root of the eukaryotes. Of the remaining MIB proteins, also DNAJC11 shows a high correlation with the presence of cristae. In mitochondrial protein complexome profiles, the MIB complex occurs as a defined complex and as separate subcomplexes, potentially reflecting various assembly stages. We find three main forms of the complex: A) The MICOS complex, containing all the MICOS proteins, B) a membrane bridging subcomplex, containing in addition SAMM50, MTX2 and the previously uncharacterized MTX3, and C) the complete MIB complex containing in addition DNAJC11 and MTX1.
authors.affiliation: Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: huynen@cmbi.ru.nl.
authors.forename: Martijn A
authors.initials: MA
authors.lastname: Huynen
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mareike
authors.initials: M
authors.lastname: Mühlmeister
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, Nijmegen, The Netherlands; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University, Germany.
authors.forename: Katherina
authors.initials: K
authors.lastname: Gotthardt
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, Nijmegen, The Netherlands; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Guerrero-Castillo
authors.affiliation: Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Center, Nijmegen, The Netherlands; Cluster of Excellence Frankfurt "Macromolecular Complexes", Goethe-University, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
mesh_terms: D045744:Cell Line, Tumor; D019143:Evolution, Molecular; D006801:Humans; D024101:Mitochondrial Proteins / Q000235:genetics*; D046912:Multiprotein Complexes / Q000235:genetics*
chemical_list: D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes
keywords: C19orf70; Complexome profiling; HemX; MIB; MICOS; Metaxin 3