Role of Tom5 in Maintaining the Structural Stability of the TOM Complex of Mitochondria

Schmitt, Simone; Ahting, Uwe; Eichacker, Lutz A.; Granvogl, Bernhard; Go, Nancy E.; Nargang, Frank E.; Neupert, Walter; Nußberger, Stephan

doi:10.1074/jbc.m413667200

Cited by 52 publications

(37 citation statements)

References 38 publications

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“…TOM Complex Stability-Alterations in the different Tom40 variants could affect the interactions between Tom40 subunits or between Tom40 and other proteins in the TOM complex. Solubilization of the TOM complex in different detergents, or different concentrations of the same detergent, has been used previously to define the more tightly interacting components of the TOM core complex or to assess the stability of the complex in mutant strains (7,8,10,11). In an attempt to measure the stability of the TOM complex in our tom40 mutants, the strains were examined qualitatively by BNGE following solubilization of isolated mitochondria with either 1% DIG or 1% DDM.…”

Section: Residues Affected By Mutationmentioning

confidence: 99%

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Effect of Mutations in Tom40 on Stability of the Translocase of the Outer Mitochondrial Membrane (TOM) Complex, Assembly of Tom40, and Import of Mitochondrial Preproteins

Sherman¹,

Taylor²,

et al. 2006

Journal of Biological Chemistry

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Mitochondrial preproteins synthesized in the cytosol are imported through the mitochondrial outer membrane by the translocase of the outer mitochondrial membrane (TOM) complex. Tom40 is the major component of the complex and is essential for cell viability. We generated 21 different mutations in conserved regions of the Neurospora crassa Tom40 protein.The mutant genes were transformed into a tom40 null nucleus maintained in a sheltered heterokaryon, and 17 of the mutant genes gave rise to viable strains. All mutations reduced the efficiency of the altered Tom40 molecules to assemble into the TOM complex. Mitochondria isolated from seven of the mutant strains had defects for importing mitochondrial preproteins. Only one strain had a general import defect for all preproteins examined. Another mutation resulted in defects in the import of a matrix-destined preprotein and an outer membrane ␤-barrel protein, but import of the ADP/ATP carrier to the inner membrane was unaffected. Five strains showed deficiencies in the import of ␤-barrel proteins. The latter results suggest that the TOM complex distinguishes ␤-barrel proteins from other classes of preprotein during import. This supports the idea that the TOM complex plays an active role in the transfer of preproteins to subsequent translocases for insertion into the correct mitochondrial subcompartment.

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Section: Residues Affected By Mutationmentioning

confidence: 99%

“…After recognition, the preproteins are passed to the TOM core complex for passage through the outer membrane. The core complex contains five different subunits: Tom40, Tom22, Tom7, Tom6, and Tom5 (7)(8)(9)(10)(11)(12).…”

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Effect of Mutations in Tom40 on Stability of the Translocase of the Outer Mitochondrial Membrane (TOM) Complex, Assembly of Tom40, and Import of Mitochondrial Preproteins

Sherman¹,

Taylor²,

et al. 2006

Journal of Biological Chemistry

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“…None of these three small proteins is essential when deleted individually. Tom5 was reported to have a function in recognizing precursor proteins and may have in addition a general role in TOM complex stability (10,42). Tom6 and Tom7 are suggested to act as antagonists in the regulation of TOM complex organization.…”

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confidence: 99%

Genetic and Functional Interactions between the Mitochondrial Outer Membrane Proteins Tom6 and Sam37

Dukanovic

Dimmer

Bonnefoy³

et al. 2009

Molecular and Cellular Biology

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The TOM complex is the general mitochondrial entry site for newly synthesized proteins. Precursors of ␤-barrel proteins initially follow this common pathway and are then relayed to the SAM/TOB complex, which mediates their integration into the outer membrane. Three proteins, Sam50 (Tob55), Sam35 (Tob38/Tom38), and Sam37 (Mas37), have been identified as the core constituents of the latter complex. Sam37 is essential for growth at elevated temperatures, but the function of the protein is currently unresolved. To identify interacting partners of Sam37 and thus shed light on its function, we screened for multicopy suppressors of sam37⌬. We identified the small subunit of the TOM complex, Tom6, as such a suppressor and found a tight genetic interaction between the two proteins. Overexpression of SAM37 suppresses the growth phenotype of tom6⌬, and cells lacking both genes are not viable. The ability of large amounts of Tom6 to suppress the sam37⌬ phenotype can be linked to the capacity of Tom6 to stabilize Tom40, an essential ␤-barrel protein which is the central component of the TOM complex. Our results suggest that Sam37 is required for growth at higher temperatures, since it enhances the biogenesis of Tom40, and this requirement can be overruled by improved stability of newly synthesized Tom40 molecules.

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“…The core complex contains the central receptor Tom22 and the channel Tom40 as well as Tom5, Tom6, and Tom7. The three small Tom proteins are involved in protein import and stability of the TOM complex (41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53), although their molecular function is only understood in part. In particular, the function of Tom7, which is well conserved in evolution, is unclear as various findings with pleiotropic and in part contradictory results have been reported.…”

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Mitochondrial Protein Sorting

Meisinger

Wiedemann

Rissler

et al. 2006

Journal of Biological Chemistry

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The mitochondrial outer membrane contains two distinct machineries for protein import and protein sorting that function in a sequential manner: the general translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex), which is dedicated to ␤-barrel proteins. The SAM core complex consists of three subunits, Sam35, Sam37, and Sam50, that can associate with a fourth subunit, the morphology component Mdm10, to form the SAM holo complex. Whereas the SAM core complex is required for the biogenesis of all ␤-barrel proteins, Mdm10 and the SAM holo complex play a selective role in ␤-barrel biogenesis by promoting assembly of Tom40 but not of porin. We report that Tom7, a conserved subunit of the TOM complex, functions in an antagonistic manner to Mdm10 in biogenesis of Tom40 and porin. We show that Tom7 promotes segregation of Mdm10 from the SAM holo complex into a low molecular mass form. Upon deletion of Tom7, the fraction of Mdm10 in the SAM holo complex is significantly increased, explaining the opposing functions of Tom7 and Mdm10 in ␤-barrel sorting. Thus the role of Tom7 is not limited to the TOM complex. Tom7 functions in mitochondrial protein biogenesis by a new mechanism, segregation of a sorting component, leading to a differentiation of ␤-barrel assembly.Mitochondria import the vast majority of their ϳ1,000 different proteins from the cytosol (1-3). Upon initial recognition and translocation by the general translocase of the outer mitochondrial membrane (TOM 5 complex), different classes of precursor proteins are distributed to the four mitochondrial subcompartments, outer membrane, intermembrane space, inner membrane, and matrix (4 -11). Preproteins carrying cleavable amino-terminal targeting signals (presequences) are transferred from the TOM complex to the presequence translocase of the inner membrane (TIM23 complex) and then sorted to matrix and inner membrane. Many mitochondrial proteins, however, are synthesized without cleavable presequences, including all outer membrane proteins and the majority of intermembrane space and inner membrane proteins. These proteins use distinct import and sorting machineries. Thus, in addition to the presequence pathway, three sorting pathways for non-cleavable mitochondrial precursor proteins have been identified, each of them starting at the TOM complex. Many hydrophobic inner membrane proteins, including the abundant metabolite carriers, are imported via small Tim proteins of the intermembrane space and the twin pore translocase of the inner membrane (TIM22 complex) (8, 12). Small proteins of the intermembrane space use a special import and assembly machinery that includes Mia40 and the sulfhydryl oxidase Erv1 (13-17). Outer membrane proteins are also initially transported via the TOM complex; however, the TOM complex is not able to integrate ␤-barrel proteins into the membrane. Therefore, the outer membrane contains a separate sorting and assembly machinery (SAM complex) that directs membrane integration and assembly of ␤-barrel...

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Role of Tom5 in Maintaining the Structural Stability of the TOM Complex of Mitochondria

Cited by 52 publications

References 38 publications

Effect of Mutations in Tom40 on Stability of the Translocase of the Outer Mitochondrial Membrane (TOM) Complex, Assembly of Tom40, and Import of Mitochondrial Preproteins

Effect of Mutations in Tom40 on Stability of the Translocase of the Outer Mitochondrial Membrane (TOM) Complex, Assembly of Tom40, and Import of Mitochondrial Preproteins

Genetic and Functional Interactions between the Mitochondrial Outer Membrane Proteins Tom6 and Sam37

Mitochondrial Protein Sorting

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