title: The ins and outs of the intermembrane space: diverse mechanisms and evolutionary rewiring of mitochondrial protein import routes.
abstract: BACKGROUND
  Mitochondrial biogenesis is an essential process in all eukaryotes. Import of proteins from the cytosol into mitochondria is a key step in organelle biogenesis. Recent evidence suggests that a given mitochondrial protein does not take the same import route in all organisms, suggesting that pathways of mitochondrial protein import can be rewired through evolution. Examples of this process so far involve proteins destined to the mitochondrial intermembrane space (IMS).
  
  
  METHODS
  Here we review the components, substrates and energy sources of the known mechanisms of protein import into the IMS. We discuss evolutionary rewiring of the IMS import routes, focusing on the example of the lactate utilisation enzyme cytochrome b2 (Cyb2) in the model yeast Saccharomyces cerevisiae and the human fungal pathogen Candida albicans.
  
  
  CONCLUSIONS
  There are multiple import pathways used for protein entry into the IMS and they form a network capable of importing a diverse range of substrates. These pathways have been rewired, possibly in response to environmental pressures, such as those found in the niches in the human body inhabited by C. albicans.
  
  
  CONCLUSIONS
  We propose that evolutionary rewiring of mitochondrial import pathways can adjust the metabolic fitness of a given species to their environmental niche. This article is part of a Special Issue entitled Frontiers of Mitochondrial.
authors.affiliation: Department of Biochemistry and Molecular Biology, Building 77, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia. Electronic address: victoria.hewitt@monash.edu.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Hewitt
authors.affiliation: Department of Biochemistry and Molecular Biology, Building 77, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia. Electronic address: kip.gabriel@monash.edu.
authors.forename: Kipros
authors.initials: K
authors.lastname: Gabriel
authors.affiliation: Department of Biochemistry and Molecular Biology, Building 77, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne 3800, Australia. Electronic address: ana.traven@monash.edu.
authors.forename: Ana
authors.initials: A
authors.lastname: Traven
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D029701:Saccharomyces cerevisiae Proteins
keywords: Conservative sorting; Folding trap; Metabolic regulation; Mitochondrial intermembrane space transport and assembly; Stop-transfer pathway; Translocation machinery