Protein targeting to and translocation across the membrane of the endoplasmic reticulum

Nunnari, Jodi; Walter, Peter

doi:10.1016/0955-0674(92)90074-m

Cited by 66 publications

(21 citation statements)

References 63 publications

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“…Most precursors that enter the secretory pathway interact with the signal recognition particle (SRP) and then undergo cotranslational translocation into the endoplasmic reticulum (Nunnari & Walter, 1992). If SRP fails to bind, chaperones of the hsp70 class associate with the nascent precursor as it emerges from the ribosome (Beckmann et al, 1990;Nelson et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

et al. 1993

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Cytochrome b2 is synthesized as a precursor in the cytoplasm and imported to the intermembrane space of yeast mitochondria. We show here that the precursor contains a tightly folded heme-binding domain and that translocation of this domain across the outer membrane requires ATP. Surprisingly, it is ATP in the mitochondrial matrix rather than external ATP that drives import of the heme-binding domain. When the folded structure of the heme-binding domain is disrupted by mutation or by urea denaturation, import and correct processing take place in ATP-depleted mitochondria. These results indicate that (1) cytochrome b2 reaches the intermembrane space without completely crossing the inner membrane, and (2) some precursors fold outside the mitochondria but remain translocation-competent, and import of these precursors in vitro does not require ATP-dependent cytosolic chaperone proteins.

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Section: Discussionmentioning

confidence: 99%

Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

et al. 1993

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“…This stage-specific cross-linking provides further evidence for the specificity of the cross-link approach used. Although it does not exclude that MIM44 is also involved in a later step (8,21,32,36,45,46). In mitochondria, a seven-subunit protein complex of the outer membrane that performs the tasks of specific recognition and membrane translocation of preproteins was identified (18,20,41 the transfer of preproteins while preventing the leakage of ions at the same time (33,44,47).…”

Section: Discussionmentioning

confidence: 99%

The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane.

Blom¹,

Kübrich²,

Rassow³

et al. 1993

Mol. Cell. Biol.

105

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The essential yeast gene MPI1 encodes a mitochondrial membrane protein that is possibly involved in protein import into the organelle (A. C. Maarse, J. Blom, L. A. Grivell, and M. Meijer, EMBO J. 11:3619-3628, 1992). For this report, we determined the submitochondrial location of the MPI1 gene product and investigated whether it plays a direct role in the translocation of preproteins. By fractionation of mitochondria, the mature protein of 44 kDa was localized to the mitochondrial inner membrane and therefore termed MIM44. Import of the precursor of MIM44 required a membrane potential across the inner membrane and involved proteolytic processing of the precursor. A preprotein in transit across the mitochondrial membranes was cross-linked to MIM44, whereas preproteins arrested on the mitochondrial surface or fully imported proteins were not cross-linked. When preproteins were arrested at two distinct stages of translocation across the inner membrane, only preproteins at an early stage of translocation could be cross-linked to MIM44. Moreover, solubilized MIM44 was found to interact with in vitro-synthesized preproteins. We conclude that MIM44 is a component of the mitochondrial inner membrane import machinery and interacts with preproteins in an early step of translocation.Only six essential genes encoding mitochondrial proteins are known in Saccharomyces cerevisiae. The products of four of these genes are located in the mitochondrial matrix: the two heat shock proteins hsp70 (6, 17) and hsp60 (5,22,35), and the two components of the mitochondrial processing peptidase (16,30,48,49). ISP42, also termed MOM38, is located in the outer membrane and forms an essential part of the mitochondrial receptor complex that is responsible for the specific recognition and translocation of preproteins (2,18,20,41,43). All of the components mentioned were found to play a crucial role in the import pathways of cytosolically synthesized preproteins.The sixth essential mitochondrial protein, encoded by MPH, has also been implicated to be involved in import of preproteins (19). The gene MPh was identified by its ability to rescue the genetic defect of a mutant impaired in mitochondrial protein import. The gene product was localized to the mitochondrial membranes by using a modified protein carrying an epitope tag. It was proposed that the protein was synthesized with an amino-terminal presequence and thus located in the inner membrane (19). The identification and characterization of the inner membrane transport machinery is currently a major goal in the analysis of mitochondrial protein import. A demonstration that the MPI1 gene product is located in the inner membrane and directly participates in the import of preproteins would be an important first step toward this goal.Here we show that the MPh gene product indeed represents a genuine component of the mitochondrial inner membrane import machinery (MIM) (27). The protein was local-* Corresponding author.ized to the inner membrane and termed MIM44. By a cross-link approach with dis...

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“…Another unresolved question is how prokaryotic membrane proteins are targeted to the cytoplasmic membrane, and what are the cellular mediators of this process. In mammalian cells, targeting of many membrane and secretory proteins is mediated by the signal recognition particle (SRP) 1 machinery (3,4). In E. coli, the targeting of secretory proteins to the inner membrane can be accomplished posttranslationally (5) with the aid of chaperones (6).…”

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confidence: 99%

FtsY, the Prokaryotic Signal Recognition Particle Receptor Homologue, Is Essential for Biogenesis of Membrane Proteins

Seluanov

Bibi

1997

Journal of Biological Chemistry

147

116

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In mammalian cells, many secretory proteins are targeted to the endoplasmic reticulum co-translationally, by the signal recognition particle (SRP) and its receptor. In Escherichia coli, the targeting of secretory proteins to the inner membrane can be accomplished post-translationally. Unexpectedly, despite this variance, E. coli contains essential genes encoding Ffh and FtsY with a significant similarity to proteins of the eukaryotic SRP machinery. In this study, we investigated the possibility that the prokaryotic SRP-like machinery is involved in biogenesis of membrane proteins in E. coli. The data presented here demonstrate that the SRP-receptor homologue, FtsY, is indeed essential for expression of integral membrane proteins in E. coli, indicating that, in the case of this group of proteins, FtsY and the mammalian SRP receptor have similar functions.

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Protein targeting to and translocation across the membrane of the endoplasmic reticulum

Cited by 66 publications

References 63 publications

Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane.

FtsY, the Prokaryotic Signal Recognition Particle Receptor Homologue, Is Essential for Biogenesis of Membrane Proteins

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Protein targeting to and translocation across the membrane of the endoplasmic reticulum

Cited by 66 publications

References 63 publications

Import of cytochrome b2 to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

Import of cytochrome b2 to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane.

FtsY, the Prokaryotic Signal Recognition Particle Receptor Homologue, Is Essential for Biogenesis of Membrane Proteins

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Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP

Import of cytochrome b₂ to the mitochondrial intermembrane space: The tightly folded heme‐binding domain makes import dependent upon matrix ATP