Recognition of preproteins by the isolated TOM complex of mitochondria

Stan, Tincuta; Ahting, Uwe; Dembowski, Markus; Künkele, Klaus‐Peter; Nußberger, Stephan; Neupert, Walter; Rapaport, Doron

doi:10.1093/emboj/19.18.4895

Cited by 79 publications

(58 citation statements)

References 41 publications

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“…This difference can be explained by variations in the lipid contents of the various complexes. We have previously reported a much higher phospholipid content in the complex isolated with digitonin as compared with the complex isolated with DDM (24).…”

Section: Tom6 and Tom7 In Neurospora Crassamentioning

confidence: 83%

Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

Dembowski

Künkele

Nargang

et al. 2001

Journal of Biological Chemistry

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Translocation of preproteins across the mitochondrial outer membrane is mediated by the translocase of the outer mitochondrial membrane (TOM) complex. We report the molecular identification of Tom6 and Tom7, two small subunits of the TOM core complex in the fungus Neurospora crassa. Cross-linking experiments showed that both proteins were found to be in direct contact with the major component of the pore, Tom40. In addition, Tom6 was observed to interact with Tom22 in a manner that depends on the presence of preproteins in transit. Precursors of both proteins are able to insert into the outer membrane in vitro and are assembled into authentic TOM complexes. The insertion pathway of these proteins shares a common binding site with the general import pathway as the assembly of both Tom6 and Tom7 was competed by a matrix-destined precursor protein. This assembly was dependent on the integrity of receptor components of the TOM machinery and is highly specific as in vitro-synthesized yeast Tom6 was not assembled into N. crassa TOM complex. The targeting and assembly information within the Tom6 sequence was found to be located in the transmembrane segment and a flanking segment toward the N-terminal, cytosolic side. A hybrid protein composed of the C-terminal domain of yeast Tom6 and the cytosolic domain of N. crassa Tom6 was targeted to the mitochondria but was not taken up into TOM complexes. Thus, both segments are required for assembly into the TOM complex. A model for the topogenesis of the small Tom subunits is discussed.

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Section: Tom6 and Tom7 In Neurospora Crassamentioning

confidence: 83%

Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

Dembowski

Künkele

Nargang

et al. 2001

Journal of Biological Chemistry

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“…Rather, it appears that different structures or functions within the complex are responsible for ensuring proper interactions between preproteins and subsequent components of the import machinery that result in proper sorting to the correct mitochondrial compartment. Import defects could result from alterations in many of the activities of the TOM complex, including movement of preproteins through the translocation pore (9,26), interactions at the cis or trans binding sites (36,63), interactions between preproteins emerging from the TOM complex and subsequent components of the import machinery (15, 41, 42, 64 -67), or alterations in the ability of the TOM complex to act as a chaperone or unfolding activity (37,38). Further work on the mutants with import defects may reveal the specific activities of the TOM complex affected.…”

Section: Tom40 Mutantsmentioning

confidence: 99%

“…Furthermore, isolated TOM complex is capable of transferring a mitochondrial presequence into the translocation pore. Tom40 is probably responsible for this process because the same transfer can be achieved by a protease-treated version of the complex, which consists mainly of Tom40 (38).…”

mentioning

confidence: 99%

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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“…Tom40 was isolated also from Neurospora crassa mitochondria. Reconstitution of these puri ed Tom40 molecules into liposomes showed that Tom40 alone is able to form a cationselective high-conductance channel, which is voltage-gated and binds mitochondrial presequences in a speci c manner (44)(45)(46)(47).…”

Section: Translocation Across the Outer Membranementioning

confidence: 99%

Protein Import Into Mitochondria

Paschen¹,

Neupert²

2001

IUBMB Life

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SummaryMost mitochondrial proteins are encoded by the nuclear genome and thus have to be imported into mitochondria from the cytosol. Protein translocation across and into the mitochondrial membranes is a multistep process facilitated by the coordinated action of at least four specialized translocation systems in the outer and inner membranes of mitochondria. The outer membrane contains one general translocase, the TOM complex, whereas three distinct translocases are located in the inner membrane, which facilitates translocation of different classes of preproteins. The TIM23 complex mediates import of matrix-targeted preproteins with Nterminal presequences, whereas hydrophobi c preproteins with internal targeting signals are inserted into the inner membrane via the TIM22 complex. The OXA translocase mediates the insertion of preproteins from the matrix space into the inner membrane. This review focuses on the structural organization and function of the import machinery of the model organisms of Saccharomyces cerevisiae and Neurospora crassa. In addition, the molecular basis of a new human mitochondrial disorder is discussed, the MohrTranebjaerg syndrome. This is the rst known disease, which is caused by an impaired mitochondrial protein import machinery leading to progressive neurodegeneration.

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Recognition of preproteins by the isolated TOM complex of mitochondria

Cited by 79 publications

References 41 publications

Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

Assembly of Tom6 and Tom7 into the TOM Core Complex ofNeurospora crassa

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

Protein Import Into Mitochondria

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