A crucial role of Mim2 in the biogenesis of mitochondrial outer membrane proteins

Dimmer, Kai Stefan; Papić, Dražen; Schumann, Benjamin; Sperl, Desirée; Krumpe, Katrin; Walther, Dirk; Rapaport, Doron

doi:10.1242/jcs.103804

Cited by 71 publications

(76 citation statements)

References 50 publications

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“…These findings suggest that Mim2 is also a substrate of Djp1. The lower content of Mim2-HA in djp1⌬ cells is probably not a secondary effect of the reduced levels of Mim1 in these cells, because Mim2-HA was observed in normal amounts in cells completely lacking Mim1 (7).…”

Section: Resultsmentioning

confidence: 88%

“…We next aimed to rule out that Djp1 is affecting Mim1 due to an unknown role of the former as part of the MIM complex that contains both Mim1 and Mim2 (7). To that end, we analyzed the MIM complex by blue native gels in the presence or absence of Djp1 and found that although the complex has reduced levels, its migration behavior is not altered (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Known members of this family in fungi include Mim1, Mim2, Tom22, and Atg32 (3)(4)(5)(6)(7). The mechanism by which these proteins are integrated into the outer membrane is largely unknown.…”

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confidence: 99%

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The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

Papić

Elbaz‐Alon

Koerdt

et al. 2013

Molecular and Cellular Biology

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A special group of mitochondrial outer membrane proteins spans the membrane once, exposing soluble domains to both sides of the membrane. These proteins are synthesized in the cytosol and then inserted into the membrane by an unknown mechanism. To identify proteins that are involved in the biogenesis of the single-span model protein Mim1, we performed a high-throughput screen in yeast. Two interesting candidates were the cytosolic cochaperone Djp1 and the mitochondrial import receptor Tom70. Our results indeed demonstrate a direct interaction of newly synthesized Mim1 molecules with Tom70. We further observed lower steady-state levels of Mim1 in mitochondria from djp1⌬ and tom70 tom71⌬ cells and massive mislocalization of overexpressed GFP-Mim1 to the endoplasmic reticulum in the absence of Djp1. Importantly, these phenotypes were observed specifically for the deletion of DJP1 and were not detected in mutant cells lacking any of the other cytosolic cochaperones of the Hsp40 family. Furthermore, the djp1⌬ tom70⌬ tom71⌬ triple deletion resulted in a severe synthetic sick/lethal growth phenotype. Taking our results together, we identified Tom70 and Djp1 as crucial players in the biogenesis of Mim1. Moreover, the involvement of Djp1 provides a unique case of specificity between a cochaperone and its substrate protein.

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

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The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

Papić

Elbaz‐Alon

Koerdt

et al. 2013

Molecular and Cellular Biology

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“…On the other hand, the MOM protein Mim1 was found to play a crucial role in the membrane integration of these proteins (4,5). In a subsequent study, the novel protein Mim2 was demonstrated to interact with Mim1 and to form with the latter the functional MIM insertase complex (6).…”

mentioning

confidence: 94%

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Sauerwald

Jores

Eisenberg-Bord

et al. 2015

Molecular and Cellular Biology

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A special group of mitochondrial outer membrane (MOM) proteins spans the membrane several times via multiple helical segments. Such multispan proteins are synthesized on cytosolic ribosomes before their targeting to mitochondria and insertion into the MOM. Previous work recognized the import receptor Tom70 and the mitochondrial import (MIM) complex, both residents of the MOM, as required for optimal biogenesis of these proteins. However, their involvement is not sufficient to explain either the entire import pathway or its regulation. To identify additional factors that are involved in the biogenesis of MOM multispan proteins, we performed complementary high-throughput visual and growth screens in Saccharomyces cerevisiae. Cardiolipin (CL) synthase (Crd1) appeared as a candidate in both screens. Our results indeed demonstrate lower steady-state levels of the multispan proteins Ugo1, Scm4, and Om14 in mitochondria from crd1⌬ cells. Importantly, MOM single-span proteins were not affected by this mutation. Furthermore, organelles lacking Crd1 had a lower in vitro capacity to import newly synthesized Ugo1 and Scm4 molecules. Crd1, which is located in the mitochondrial inner membrane, condenses phosphatidylglycerol together with CDP-diacylglycerol to obtain de novo synthesized CL molecules. Hence, our findings suggest that CL is an important component in the biogenesis of MOM multispan proteins.

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“…The mechanisms of insertion of these proteins into the outer membrane are only understood in part. The mitochondrial import (MIM) complex has been found to support membrane insertion of a number of outer membrane proteins, in particular proteins with amino-terminal or multiple transmembrane segments (Becker et al, , 2011aPopov-Čeleketić et al, 2008b;Hulett et al, 2008;Papić et al, 2011;Dimmer et al, 2012;Wenz et al, 2014). TOM receptors can help in the recognition of α-helical precursor proteins.…”

Section: Principles Of Mitochondrial Protein Importmentioning

confidence: 99%

Dynamic organization of the mitochondrial protein import machinery

Straub

Stiller

Wiedemann

et al. 2016

Biological Chemistry

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Mitochondria contain elaborate machineries for the import of precursor proteins from the cytosol. The translocase of the outer mitochondrial membrane (TOM) performs the initial import of precursor proteins and transfers the precursors to downstream translocases, including the presequence translocase and the carrier translocase of the inner membrane, the mitochondrial import and assembly machinery of the intermembrane space, and the sorting and assembly machinery of the outer membrane. Although the protein translocases can function as separate entities in vitro, recent studies revealed a close and dynamic cooperation of the protein import machineries to facilitate efficient transfer of precursor proteins in vivo. In addition, protein translocases were found to transiently interact with distinct machineries that function in the respiratory chain or in the maintenance of mitochondrial membrane architecture. Mitochondrial protein import is embedded in a regulatory network that ensures protein biogenesis, membrane dynamics, bioenergetic activity and quality control.

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A crucial role of Mim2 in the biogenesis of mitochondrial outer membrane proteins

Cited by 71 publications

References 50 publications

The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

The Role of Djp1 in Import of the Mitochondrial Protein Mim1 Demonstrates Specificity between a Cochaperone and Its Substrate Protein

Genome-Wide Screens in Saccharomyces cerevisiae Highlight a Role for Cardiolipin in Biogenesis of Mitochondrial Outer Membrane Multispan Proteins

Dynamic organization of the mitochondrial protein import machinery

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