InterPro domain: IPR027246

This entry represents both eukaryotic mitochondrial porins and Tom40 proteins.

Eukaryotic mitochondrial porins are voltage-dependent anion-selective channels (VDAC) that behave as general diffusion pores for small hydrophilic molecules [ 1 , 2 , 3 , 4 ]. The channels adopt an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The eukaryotic mitochondrial porins are beta-barrel proteins, composed of between 12 to 16 beta-strands that span the mitochondrial outer membrane. Yeast contains two members of this family (genes POR1 and POR2); vertebrates have at least three members (genes VDAC1, VDAC2 and VDAC3) [ 5 ]. They are related to the mitochondrial import receptor subunit Tom40 proteins, sharing a common evolutionary origin and structure [ 6 ].

Tom40 is a mitochondrion outer membrane protein and a component of the TOM (translocator of the outer mitochondrial membrane) complex, which is essential for import of protein precursors into mitochondria [ 7 ]. In Saccharomyces cerevisiae, TOM complex is composed of the subunits Tom70, Tom40, Tom22, Tom20, Tom7, Tom6, and Tom5 [ 8 , 9 ]. Tom40 is an integral membrane protein and the main structural component of the protein-conducting channel formed by the TOM complex [ 10 ]. It is stabilised by other components, such as Tom5, Tom6, and Tom7 [ 11 ].

1. Permeation of hydrophilic solutes through mitochondrial outer membranes: review on mitochondrial porins. Biochim. Biophys. Acta 1197, 167-96
2. The 'ins' and 'outs' of mitochondrial membrane channels. Trends Biochem. Sci. 17, 315-20
3. The biogenesis and function of eukaryotic porins. Experientia 46, 146-53
4. Molecular genetics of the VDAC ion channel: structural model and sequence analysis. J. Bioenerg. Biomembr. 19, 341-50
5. A novel mouse mitochondrial voltage-dependent anion channel gene localizes to chromosome 8. Genomics 36, 192-6
6. Phylogenetic and coevolutionary analysis of the β-barrel protein family comprised of mitochondrial porin (VDAC) and Tom40. Biochim. Biophys. Acta 1818, 1502-19
7. Biogenesis of Tom40, core component of the TOM complex of mitochondria. J. Cell Biol. 146, 321-31
8. Identification of the mitochondrial receptor complex in Saccharomyces cerevisiae. FEBS Lett. 310, 265-8
9. Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Mol. Cell. Biol. 18, 6515-24
10. Tom40 protein import channel binds to non-native proteins and prevents their aggregation. Nat. Struct. Biol. 10, 988-94
11. Protein translocase of the outer mitochondrial membrane: role of import receptors in the structural organization of the TOM complex. J. Mol. Biol. 316, 657-66