Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex

Schulz, Christian; Lytovchenko, Oleksandr; Melin, Jonathan; Chacińska, Agnieszka; Guiard, Bernard; Neumann, Piotr; Ficner, Ralf; Jahn, Olaf; Schmidt, Bernhard; Rehling, Peter

doi:10.1083/jcb.201105098

Cited by 88 publications

(162 citation statements)

References 44 publications

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“…Accumulation of Om45-DHFR in the TOM complex depended on these subunits of the presequence translocase in a manner comparable to the accumulation of the cleavable preprotein Oxa1 in TOM (Fig 3E) [29]. Import of Om45 32 A, B [ 35 S]Om45 was imported into WT and mutant mitochondria as described in the legend of Fig 1B and Fig S2E), indicating that the presequence translocase is involved in import of the large C-terminal domain of Om45 into the intermembrane space. We conclude that the presequence translocase of the inner membrane is required for the import of Om45.…”

Section: Import Of Om45 Uses Elements Of the Presequence Pathwaymentioning

confidence: 83%

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The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

et al. 2014

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The mitochondrial outer membrane contains integral a-helical and b-barrel proteins that are imported from the cytosol. The machineries importing b-barrel proteins have been identified, however, different views exist on the import of a-helical proteins. It has been reported that the biogenesis of Om45, the most abundant signal-anchored protein, does not depend on proteinaceous components, but involves direct insertion into the outer membrane. We show that import of Om45 occurs via the translocase of the outer membrane and the presequence translocase of the inner membrane. Assembly of Om45 in the outer membrane involves the MIM machinery. Om45 thus follows a new mitochondrial biogenesis pathway that uses elements of the presequence import pathway to direct a protein to the outer membrane.

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Section: Import Of Om45 Uses Elements Of the Presequence Pathwaymentioning

confidence: 83%

“…We thus analysed mutant mitochondria, which are impaired in subunits of the TIM23 complex [29][30][31][32]. Conditional mutants of the essential subunits Tim23, Tim50 and Tim17 were considerably impaired in the import of Om45 (Fig 3B and C).…”

Section: Import Of Om45 Uses Elements Of the Presequence Pathwaymentioning

confidence: 99%

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

et al. 2014

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“…2). The first subunit of the TIM23 complex encountered by an incoming precursor protein on the trans-side of the TOM complex is Tim50 (26)(27)(28)(29). Tim50 passes the presequence to the channel forming unit of TIM23 formed by the Tim23 and Tim17 proteins.…”

Section: Figmentioning

confidence: 99%

Mitochondrial protein homeostasis

2013

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Mitochondria use 800-1,500 proteins to perform their biological functions in the eukaryotic cells. Distinct transport and sorting mechanisms are responsible for the delivery of proteins to the correct location within mitochondria. Mitochondrial proteins undergo processing events and form functional assemblies.Finally, non-functional proteins are cleared to maintain healthy mitochondria. We provide an overview of the processes collectively contributing to the maintenance of mitochondrial protein homeostasis, which is critical for cell physiology and survival.

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“…To characterize presequence binding of the C-terminal PBD of yeast Tim50 by NMR, we recorded NMR spectra of several recombinant constructs derived from the previously suggested Tim50 PBD (residues 395-476) [9] (Fig. 1A, upper panel) in the absence of a presequence peptide.…”

Section: Nmr Spectrum Of Spbdmentioning

confidence: 99%

“…The determined X-ray structure of residues 176-361 consists of five a-helices and nine b-strands, and a negatively charged groove near the protruding b-hairpin was proposed to bind to a positively charged presequence [8]. Interestingly, the presence of a presequence binding site was reported for not only the conserved core domain (residues 164-361) but also the C-terminal ''presequence binding'' domain (PBD: residues 395-476) in yeast Tim50 [9,10]. Abbreviations: IMS, intermembrane space; PBD, presequence binding domain; sPBD, a shorter variant of PBD; Tim50core, Tim50 core domain; pSu9N, the N-terminal half of the presequence of subunit 9 of F o -ATPase; pHsp60, the presequence of mitochondrial Hsp60…”

Section: Introductionmentioning

confidence: 99%

NMR analyses on the interactions of the yeast Tim50 C‐terminal region with the presequence and Tim50 core domain

et al. 2014

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a b s t r a c tThe mitochondrial targeting signal in the presequence of mitochondrial precursor proteins is recognized by Tom20 and subsequently by Tim50 in mitochondria. Yeast Tim50 contains two presequence binding sites in the conserved core domain and in the fungi-specific C-terminal presequence binding domain (PBD). We report the NMR analyses on interactions of a shorter variant of PBD (sPBD), a shorter variant of PBD, with presequences. The presequence is recognized by sPBD in a similar manner to Tom20. sPBD can also bind to the core domain of Tim50 through the presequence binding region, which could promote transfer of the presequence from sPBD to the core domain in Tim50. Structured summary of protein interactions:Tim50 sPBD and Tim50core bind by nuclear magnetic resonance (View interaction) pSu9N and Tim50 sPBD bind by nuclear magnetic resonance (1, 2, 3, 4, 5) pSu9N and dTim20 bind by nuclear magnetic resonance (View interaction)

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Tim50’s presequence receptor domain is essential for signal driven transport across the TIM23 complex

Abstract: The Tim50 subunit of the mitochondrial TIM23 complex contains a presequence-binding domain that is essential for viability and precursor transport across the inner membrane.

Cited by 88 publications

References 44 publications

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

Mitochondrial protein homeostasis

NMR analyses on the interactions of the yeast Tim50 C‐terminal region with the presequence and Tim50 core domain

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