Protein import into yeast mitochondria: the inner membrane import site protein ISP45 is the MPI1 gene product.

Horst, Martin; Jenö, Paul; Kronidou, Nafsika G.; Bolliger, Luca; Oppliger, Wolfgang; Scherer, Philipp E.; Manning-Krieg, Ute C.; Jascur, Thomas; Schatz, Gottfried

doi:10.1002/j.1460-2075.1993.tb05972.x

Cited by 79 publications

(36 citation statements)

References 26 publications

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“…Beginning with mitochondrial membranes and/or contact sites, reverse genetics has been used to identify genes encoding receptors and the translocation channel (8,31,36,40,55,70,71). Other components of the yeast mitochondrial import apparatus have been identified via multicopy suppressors of mutations of genes encoding components of the contact sites (39), by selecting for mutants not able to import particular gene fusion proteins to mitochondria (36,47), or by screening temperature-sensitive mutants for defects in mitochondrial import (23,62). Surprisingly, besides components of the heat shock response (reviewed in reference 72) the genetic screens and selections have failed to identify cytoplasmic proteins that play a role in mitochondrial import.…”

Section: Discussionmentioning

confidence: 99%

Mutations Altering the Mitochondrial-Cytoplasmic Distribution of Mod5p Implicate the Actin Cytoskeleton and mRNA 3′ Ends and/or Protein Synthesis in Mitochondrial Delivery

Żołądek

Vaduva

Hunter

et al. 1995

Molecular and Cellular Biology

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). A mutant allele of MOD5 encoding a protein (Mod5p-I,KR6) located predominantly in mitochondria was constructed. Mutants defective in delivering Mod5p-I,KR6 to mitochondria were sought by selecting cells with increased cytosolic activity of this protein. Twenty-five mutants defining four complementation groups, mdp1, mdp2, mdp3, and mdp4, were found. They are unable to respire at 34؇C or to grow on glucose medium at 38؇C. Cell fractionation studies showed that mdp1, mdp2, and mdp3 mutants have an altered mitochondrial-cytoplasmic distribution of Mod5p. mdp2 can be suppressed by ACT1, the actin-encoding gene. The actin cytoskeleton organization is also aberrant in mdp2 cells. MDP2 is the same as VRP1 (S. Eukaryotic cells have organelles separated physically from one another by lipid bilayers and the cytosol. Most proteins have a single destination such as the nucleus, mitochondria, peroxisomes, lysosomes, or the cell surface. However, we and others have discovered a class of genes that encode sorting isozymes, enzymes found in more than one cellular compartment (references 9, 10, 13, 18, 22, 34, 49, and 50; see also references cited in references 28 and 80).The Saccharomyces cerevisiae MOD5 and CCA1 genes that encode the tRNA processing enzymes N 6 -(⌬ 2 )-isopentenyl PP i : tRNA isopentenyltransferase (IPP transferase) and ATP (CTP):tRNA nucleotidyltransferase, respectively, are unique in that the sorting isozymes they encode are found in two organelles (mitochondria and nuclei) as well as the cytosol (10, 79, 80). MOD5 codes for two proteins that differ from each other by the presence or absence of an amino-terminal extension (28,69). Translation initiation at the first AUG of the open reading frame (ORF) produces Mod5p-I, which is located in mitochondria and the cytosol; translation initiation at the second AUG at codon 12 gives rise to Mod5p-II, located in the cytosol and nucleus (10).The mechanisms that locate proteins to single subcellular destinations have been intensively investigated. The importance of cis-acting sequences on the proteins is clearly established. Inroads are being made in identifying components on the organelles that serve as receptors and import channels. Cytosolic factors play critical roles (for an example, see review in reference 72), and recent observations suggest that the site of a protein's synthesis can also be an important factor in dictating its final destination (reviewed in reference 77). Despite this general outline of protein location, there is a very incomplete understanding of how the cell manages intracellular traffic. The natural distribution and function of sorting isozymes in multiple cellular compartments should provide a powerful tool to apply new genetic approaches to studies of protein delivery. This is because the distribution of sorting isozymes is balanced between multiple destinations, and the balance can be altered by cis-acting mutations as shown by the phenotypes caused by changing ATGs of MOD5 and CCA1 (10,28,80). The balance should also be altered by mu...

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Section: Discussionmentioning

confidence: 99%

Mutations Altering the Mitochondrial-Cytoplasmic Distribution of Mod5p Implicate the Actin Cytoskeleton and mRNA 3′ Ends and/or Protein Synthesis in Mitochondrial Delivery

Żołądek

Vaduva

Hunter

et al. 1995

Molecular and Cellular Biology

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“…MPI1 has been identified as the first protein of the inner membrane involved in precursor import [20][21][22]. MPI1 or ISP45 was later renamed MIM44 to make clear that it is an inner membrane protein.…”

Section: The Import Machinery Of the Inner Membranementioning

confidence: 99%

Mitochondrial protein import: Mechanisms, components and energetics

Schwarz

Neupert

1994

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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The transport of nuclear-encoded proteins from the cytosol into mitochondria is mediated by targeting (signal) sequences present on precursor forms. Most precursors of the mitochondrial matrix possess amino-terminal signals which characteristically contain hydroxylated and basic amino acids and lack acidic residues. With a minority of precursor proteins, internal sequence motifs can direct proteins to the mitochondria (Planner, N., Hoeben, P., Tropschug, M. and Neupert, W. (1987) J. Biol. Chem. 262, 14851-14854). The presence of a mitochondrial targeting sequence alone, however, is not sufficient for specific targeting to the organeUe and further to the various subcompartments. There is the need for components which recognise the targeting sequences and others which keep the precursor protein in a translocation-competent form. Beyond the recognition step, components are required which mediate transiocation across the mitochondrial membranes. Mitochondria possess two translocation machineries, one in the outer membrane and one in the inner membrane. The matrix space harbors a number of factors which participate in the import of proteins, in their unfolding and folding. Energy is required at several steps of these processes.

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“…Import of presequence targeted proteins into the mitochondrial matrix generally requires a membrane potential (⌬ ) across the mitochondrial inner membrane and the TIM17-23 translocase machinery (10 -14). The TIM17-23 translocase, along with the membrane-bound TIM44 and the matrix chaperone mt-Hsp70 (15)(16)(17)(18)(19)(20)(21), mediate the translocation across the inner membrane into the matrix. Alternatively, import of several inner membrane proteins, such as the ADP/ATP carrier and components of the TIM machinery itself, is mediated by the TIM22-54 translocase (22)(23)(24).…”

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confidence: 99%

The DNA Helicase, Hmi1p, Is Transported into Mitochondria by a C-terminal Cleavable Targeting Signal

Lee

Sedman

Neupert

et al. 1999

Journal of Biological Chemistry

104

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We have identified a novel mitochondrial targeting signal in the precursor of the DNA helicase Hmi1p of Saccharomyces cerevisiae that is located at the C terminus of the protein. Similar to classical N-terminal presequences, this C-terminal targeting signal consists of a stretch of positively charged amino acids that has the potential to form an amphipathic ␣-helix. Deletion of the C-terminal 36 amino acids of helicase resulted in loss of import into mitochondria, while deletion of the N-terminal 40 amino acids had no effect. When C-terminal regions of the helicase were placed at the C terminus of a passenger protein, dihydrofolate reductase, the resulting fusion proteins were directed into the mitochondrial matrix, and the C-terminal region of helicase became proteolytically processed. Import of helicase occurs in a C-to N-terminal direction; it requires a membrane potential and the TIM17-23 translocase together with mitochondrial Hsp70. Helicase is the only mitochondrial matrix protein identified thus far with a cleavable targeting signal at its C terminus.

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Protein import into yeast mitochondria: the inner membrane import site protein ISP45 is the MPI1 gene product.

Cited by 79 publications

References 26 publications

Mutations Altering the Mitochondrial-Cytoplasmic Distribution of Mod5p Implicate the Actin Cytoskeleton and mRNA 3′ Ends and/or Protein Synthesis in Mitochondrial Delivery

Mutations Altering the Mitochondrial-Cytoplasmic Distribution of Mod5p Implicate the Actin Cytoskeleton and mRNA 3′ Ends and/or Protein Synthesis in Mitochondrial Delivery

Mitochondrial protein import: Mechanisms, components and energetics

The DNA Helicase, Hmi1p, Is Transported into Mitochondria by a C-terminal Cleavable Targeting Signal

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