Structure, topology and function of the translocase of the outer membrane of mitochondria

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Background: Nearly all nascent mitochondrial proteins are transported by the translocase of the outer membrane (TOM) complex. Results:The core Tom40 ␤-barrel domain exhibits four conductive levels and three distinct substrate binding affinities. Conclusion: Tom40 interactions with presequence substrates depend upon the channel's conformation. Significance: Conformational rearrangements in Tom40 may regulate substrate interactions.

mentioning

confidence: 76%

Evidence of Distinct Channel Conformations and Substrate Binding Affinities for the Mitochondrial Outer Membrane Protein Translocase Pore Tom40

Kuszak

Jacobs

Gurnev

et al. 2015

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“…The TOM complex of both Saccharomyces cerevisiae and Neurospora crassa consists of five core proteins (Tom40, Tom22, Tom7, Tom6, and Tom5) and two receptors (Tom70 and Tom20) that are more loosely associated. The TOM complex of animals is quite similar to the fungal version, whereas the plant complex contains several different subunits (8,9). Although some of the components of the TOM complex may vary in different organisms, the Tom40 protein is highly conserved (10 -13).…”

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confidence: 99%

Evidence Supporting the 19 β-Strand Model for Tom40 from Cysteine Scanning and Protease Site Accessibility Studies

Lackey

Taylor

et al. 2014

Background: Tom40 has been modeled as a 19-strand ␤-barrel after the three-dimensional structure of porin. However, a 13-strand model for porin also exists. Results: Several ␤-strands were mapped in Tom40, all are predicted by the 19-strand model. Conclusion: Data support the 19-strand model for Tom40. Significance: Predictions relating the Tom40 structure and function can be made with more confidence.

“…In A. thaliana (and by inference plants in general) the outermembrane receptor components differ from the yeast and mammalian systems. The plant outermembrane Tom20 and OM64 proteins are not orthologous to yeast Tom20 and Tom70 (22,(67)(68)(69). Although A. thaliana Mia40 may be orthologous to yeast Mia40, it differs in function (and location).…”

Section: Discussionmentioning

confidence: 99%

Conserved and Novel Functions for Arabidopsis thaliana MIA40 in Assembly of Proteins in Mitochondria and Peroxisomes

Carrie

Giraud

Duncan

et al. 2010

100

113

The disulfide relay system of the mitochondrial intermembrane space has been extensively characterized in Saccharomyces cerevisiae. It contains two essential components, Mia40 and Erv1. The genome of Arabidopsis thaliana contains a single gene for each of these components. Although insertional inactivation of Erv1 leads to a lethal phenotype, inactivation of Mia40 results in no detectable deleterious phenotype. A. thaliana Mia40 is targeted to and accumulates in mitochondria and peroxisomes. Inactivation of Mia40 results in an alteration of several proteins in mitochondria, an absence of copper/zinc superoxide dismutase (CSD1), the chaperone for superoxide dismutase (Ccs1) that inserts copper into CSD1, and a decrease in capacity and amount of complex I. In peroxisomes the absence of Mia40 leads to an absence of CSD3 and a decrease in abnormal inflorescence meristem 1 (Aim1), a ␤-oxidation pathway enzyme. Inactivation of Mia40 leads to an alteration of the transcriptome of A. thaliana, with genes encoding peroxisomal proteins, redox functions, and biotic stress significantly changing in abundance. Thus, the mechanistic operation of the mitochondrial disulfide relay system is different in A. thaliana compared with other systems, and Mia40 has taken on new roles in peroxisomes and mitochondria.Characterization of the proteomes of mitochondria from Saccharomyces cerevisiae (yeast), mammals, and plants indicates that they contain from 1000 proteins in yeast to ϳ2000 in higher organisms (1). As the coding capacity of mitochondria is limited to between 8 and approximately 50 proteins in yeast and plants, respectively (2), the majority of mitochondrial proteins are encoded by nuclear located genes, translated in the cytosol, and imported into mitochondria. The import of hundreds of different proteins is achieved by the combined action of a number of multisubunit, integral membrane protein complexes, known as translocases. These translocases work in conjunction with a variety of soluble components located in the cytosol, intermembrane space, and mitochondrial matrix, such as chaperones, peptidases, and assembly factors (3, 4).The outer mitochondrial membrane contains the TOM complex (translocase of the outer membrane) and the sorting and assembly machinery; the latter is also known as the TOB complex (topogenesis of ␤-barrel proteins) (4). Almost all mitochondrial proteins are initially recognized by the outer membrane complex and are passed to other components depending on their final location. ␤-Barrel proteins of the outer membrane such as Tom40 and voltage-dependent anion channel protein (VDAC) are passed to the sorting and assembly machinery complex (5). Proteins imported via the general and carrier import pathways are passed to the translocases of the inner membrane 23 (TIM23) and 22 (TIM22), respectively (3, 4). Proteins are passed to the TIM23 complex directly from the outer membrane complex with the aid of Tim50 (6, 7) and also possibly Tim23, where the N-terminal region has been shown to transiently associate ...