title: A model system for mitochondrial biogenesis reveals evolutionary rewiring of protein import and membrane assembly pathways.
abstract: The controlled biogenesis of mitochondria is a key cellular system coordinated with the cell division cycle, and major efforts in systems biology currently are directed toward understanding of the control points at which this coordination is achieved. Here we present insights into the function, evolution, and regulation of mitochondrial biogenesis through the study of the protein import machinery in the human fungal pathogen, Candida albicans. Features that distinguish C. albicans from baker's yeast (Saccharomyces cerevisiae) include the stringency of metabolic control at the level of oxygen consumption, the potential for ATP exchange through the porin in the outer membrane, and components and domains in the sorting and assembling machinery complex, a molecular machine that drives the assembly of proteins in the outer mitochondrial membrane. Analysis of targeting sequences and assays of mitochondrial protein import show that components of the electron transport chain are imported by distinct pathways in C. albicans and S. cerevisiae, representing an evolutionary rewiring of mitochondrial import pathways. We suggest that studies using this pathogen as a model system for mitochondrial biogenesis will greatly enhance our knowledge of how mitochondria are made and controlled through the course of the cell-division cycle.
authors.affiliation: Department of Biochemistry and Molecular Biology and Victorian Bioinformatics Consortium,  Monash University, Melbourne, VIC 3800,  Australia.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Hewitt
authors.forename: Eva
authors.initials: E
authors.lastname: Heinz
authors.forename: Miguel
authors.initials: M
authors.lastname: Shingu-Vazquez
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.forename: Branka
authors.initials: B
authors.lastname: Jelicic
authors.forename: Tricia L
authors.initials: TL
authors.lastname: Lo
authors.forename: Traude H
authors.initials: TH
authors.lastname: Beilharz
authors.forename: Geoff
authors.initials: G
authors.lastname: Dumsday
authors.forename: Kipros
authors.initials: K
authors.lastname: Gabriel
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
authors.forename: Trevor
authors.initials: T
authors.lastname: Lithgow
mesh_terms: D005075:Biological Evolution; D002176:Candida albicans / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D008390:Markov Chains; D008928:Mitochondria / Q000502:physiology*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008954:Models, Biological; D010101:Oxygen Consumption / Q000502:physiology; D010802:Phylogeny; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D045222:Electron Transport Chain Complex Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins