The three domains of the mitochondrial outer membrane protein Mim1 have discrete functions in assembly of the TOM complex

Lueder, Franziska B; Lithgow, Trevor

doi:10.1016/j.febslet.2009.03.064

Cited by 29 publications

(34 citation statements)

References 37 publications

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“…However, as Tom22 is a core component of the TOM complex, its biogenesis mechanism probably reflects a specific case and does not provide a general paradigm for other proteins from this group. Previous studies have shown that the cytosolic domains of Tom22 and Mim1 are not required for their targeting to and insertion into the MOM (8,10,11). Following these findings, it has been assumed that the transmembrane segment and its flanking regions serve as a targeting signal to the organelle.…”

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confidence: 98%

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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mentioning

confidence: 98%

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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“…The Mim1 C-terminal domain is exposed to the cytoplasm (Lueder and Lithgow 2009;Walther and Rapaport 2009). The pathway that Mim1 takes into the outer membrane has not yet been studied.…”

Section: Import and Insertion Of B-barrel Proteinsmentioning

confidence: 99%

Mitochondrial Protein Synthesis, Import, and Assembly

2012

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The mitochondrion is arguably the most complex organelle in the budding yeast cell cytoplasm. It is essential for viability as well as respiratory growth. Its innermost aqueous compartment, the matrix, is bounded by the highly structured inner membrane, which in turn is bounded by the intermembrane space and the outer membrane. Approximately 1000 proteins are present in these organelles, of which eight major constituents are coded and synthesized in the matrix. The import of mitochondrial proteins synthesized in the cytoplasm, and their direction to the correct soluble compartments, correct membranes, and correct membrane surfaces/topologies, involves multiple pathways and macromolecular machines. The targeting of some, but not all, cytoplasmically synthesized mitochondrial proteins begins with translation of messenger RNAs localized to the organelle. Most proteins then pass through the translocase of the outer membrane to the intermembrane space, where divergent pathways sort them to the outer membrane, inner membrane, and matrix or trap them in the intermembrane space. Roughly 25% of mitochondrial proteins participate in maintenance or expression of the organellar genome at the inner surface of the inner membrane, providing 7 membrane proteins whose synthesis nucleates the assembly of three respiratory complexes.

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“…It is tempting to speculate that the kinetoplastid-specific pATOM36 might be a functional analogue of fungal Mim1 and -2, which were shown to be involved in the insertion and/or assembly of some signal-anchored OM proteins in yeast (22,23,44,45). Thus, although the targeting signals for signal-anchored proteins appear to be conserved in all eukaryotes, this is not the case for the factors mediating their biogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it has been demonstrated that the pore protein Tom40 can be blocked without affecting the import of signal-anchored proteins, although Tom20 still requires Tom40 for its biogenesis (9 -11). Finally, a protein complex consisting of Mim1 and Mim2 has been characterized that is involved in import and assembly of at least some signalanchored OM proteins (22,23,44,45). Mim1 and Mim2 were also shown to be involved in the insertion and/or assembly of some tail-anchored as well as multimembrane-spanning proteins.…”

Section: Discussionmentioning

confidence: 99%

Biogenesis of a Mitochondrial Outer Membrane Protein in Trypanosoma brucei: TARGETING SIGNAL AND DEPENDENCE ON A UNIQUE BIOGENESIS FACTOR

Bruggisser

Käser

Mani

et al. 2017

Journal of Biological Chemistry

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Edited by Thomas SöllnerThe mitochondrial outer membrane (OM) contains single and multiple membrane-spanning proteins that need to contain signals that ensure correct targeting and insertion into the OM. The biogenesis of such proteins has so far essentially only been studied in yeast and related organisms. Here we show that POMP10, an OM protein of the early diverging protozoan Trypanosoma brucei, is signal-anchored. Transgenic cells expressing variants of POMP10 fused to GFP demonstrate that the N-terminal membrane-spanning domain flanked by a few positively charged or neutral residues is both necessary and sufficient for mitochondrial targeting. Carbonate extraction experiments indicate that although the presence of neutral instead of positively charged residues did not interfere with POMP10 localization, it weakened its interaction with the OM. Expression of GFP-tagged POMP10 in inducible RNAi cell lines shows that its mitochondrial localization depends on pATOM36 but does not require Sam50 or ATOM40, the trypanosomal analogue of the Tom40 import pore. pATOM36 is a kinetoplastid-specific OM protein that has previously been implicated in the assembly of OM proteins and in mitochondrial DNA inheritance. In summary, our results show that although the features of the targeting signal in signal-anchored proteins are widely conserved, the protein machinery that mediates their biogenesis is not.Mitochondria perform many important functions and are essential for all eukaryotes (1). Whereas a small number of proteins are synthesized in the organelle, Ͼ95% of the mitochondrial proteome is nuclear-encoded, synthesized in the cytosol, and subsequently imported into mitochondria (2-4). Mitochondria consist of four compartments: the outer and the inner membrane that surround the soluble intermembrane space (IMS) 2 and the matrix, respectively. Thus, nuclear-encoded proteins not only need to be targeted to mitochondria but also sorted to their correct intra-mitochondrial destination. The mitochondrial outer membrane (OM) is of special interest. It builds the interface between the organelle and the cytosol and forms a barrier across which all communication between the organelle and its surroundings must occur (5-7). Mitochondrial OM proteins mediate apoptosis, fission, fusion and interaction with other organelles as well as transport of metabolites and precursor proteins. Whereas mitochondrial protein import in general has been extensively studied, we still have large gaps in the understanding of the biogenesis of mitochondrial OM proteins (8 -11).Integral OM proteins are either anchored by a transmembrane ␤-barrel or by single or multiple ␣-helices. The single membrane-spanning proteins can be further categorized into N-terminal (signal)-anchored, internally anchored or C-terminal (tail)-anchored proteins. OM proteins generally contain internal targeting signals. For ␤-barrel proteins the OM targeting signal appears to be a dedicated ␤-hairpin motif (12), whereas for single membrane-spanning proteins the targeting signal...

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The three domains of the mitochondrial outer membrane protein Mim1 have discrete functions in assembly of the TOM complex

Cited by 29 publications

References 37 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

Mitochondrial Protein Synthesis, Import, and Assembly

Biogenesis of a Mitochondrial Outer Membrane Protein in Trypanosoma brucei: TARGETING SIGNAL AND DEPENDENCE ON A UNIQUE BIOGENESIS FACTOR

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