Phylogenetic and coevolutionary analysis of the β-barrel protein family comprised of mitochondrial porin (VDAC) and Tom40

Biochim Biophys Acta. 2012 Jun;1818(6):1502-19. doi: 10.1016/j.bbamem.2011.11.027. Epub 2011 Dec 4.


Beta-barrel proteins are the main transit points across the mitochondrial outer membrane. Mitochondrial porin, the voltage-dependent, anion-selective channel (VDAC), is responsible for the passage of small molecules between the mitochondrion and the cytosol. Through interactions with other mitochondrial and cellular proteins, it is involved in regulating organellar and cellular metabolism and likely contributes to mitochondrial structure. Tom40 is part of the translocase of the outer membrane, and acts as the channel for passage of preproteins during their import into the organelle. These proteins appear to share a common evolutionary origin and structure. In the current study, the evolutionary relationships between and within both proteins were investigated through phylogenetic analysis. The two groups have a common origin and have followed independent, complex evolutionary pathways, leading to the generation of paralogues in animals and plants. Structures of diverse representatives were modeled, revealing common themes rather than sites of high identity in both groups. Within each group, intramolecular coevolution was assessed, revealing a new set of sites potentially involved in structure-function relationships in these molecules. A weak link between Tom40 and proteins related to the mitochondrial distribution and morphology protein, Mdm10, was identified. This article is part of a Special Issue entitled: VDAC structure, function, and regulation of mitochondrial metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Evolution, Molecular*
  • Humans
  • Mitochondrial Proteins / chemistry*
  • Mitochondrial Proteins / genetics*
  • Models, Molecular
  • Molecular Sequence Data
  • Phylogeny*
  • Protein Structure, Secondary
  • Voltage-Dependent Anion Channels / chemistry*
  • Voltage-Dependent Anion Channels / genetics*


  • Mitochondrial Proteins
  • Voltage-Dependent Anion Channels