Mitochondrial Protein Sorting

Meisinger, Chris; Wiedemann, Nils; Rissler, Michael; Strub, Andreas; Milenkovic, Dusanka; Schönfisch, Birgit; Müller, H.; Kozjak, Vera; Pfanner, Nikolaus

doi:10.1074/jbc.m602679200

Cited by 91 publications

(55 citation statements)

References 70 publications

(45 reference statements)

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“…The ER-mitochondria encounter structure (ERMES), also involved in ER-mitochondria tethering, is a multifunctional protein complex implicated in both lipid transfer and mitochondrial outer membrane protein assembly ( AhYoung et al , 2015; Kornmann et al , 2009; Meisinger et al , 2006, Meisinger et al , 2007; Wideman et al , 2013; Wideman et al , 2010). However, ERMES as an ER-mitochondria tether is limited to a subset of eukaryote taxa ( Wideman et al , 2013), suggesting that a universal ER-mitochondria tethering complex might exist.…”

Section: Introductionmentioning

confidence: 99%

The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?

Wideman

2015

F1000Res

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The recently discovered endoplasmic reticulum (ER) membrane protein complex (EMC) has been implicated in ER-associated degradation (ERAD), lipid transport and tethering between the ER and mitochondrial outer membranes, and assembly of multipass ER-membrane proteins. The EMC has been studied in both animals and fungi but its presence outside the Opisthokont clade (animals + fungi + related protists) has not been demonstrated. Here, using homology-searching algorithms, I show that the EMC is truly an ancient and conserved protein complex, present in every major eukaryotic lineage. Very few organisms have completely lost the EMC, and most, even over 2 billion years of eukaryote evolution, have retained a majority of the complex members. I identify Sop4 and YDR056C in Saccharomyces cerevisiae as Emc7 and Emc10, respectively, subunits previously thought to be specific to animals. This study demonstrates that the EMC was present in the last eukaryote common ancestor (LECA) and is an extremely important component of eukaryotic cells even though its primary function remains elusive.

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Section: Introductionmentioning

confidence: 99%

The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?

Wideman

2015

F1000Res

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“…Then the intermembrane space domain of Tom7 was found to constitute the trans site for presequence binding to facilitate efficient translocation of presequencecontaining precursor proteins across the outer membrane (23). Recently, Tom7 was found to affect association of Mdm10 with the TOB core complex, which results in sequestration of Mdm10 from formation of the TOB holo complex (24). We found that depletion or overexpression of Tom7 prevents Tom40 from association with or dissociation from the TOB complex, respectively, by regulating the association of Mdm10 with the TOB complex.…”

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confidence: 99%

Tom7 Regulates Mdm10-mediated Assembly of the Mitochondrial Import Channel Protein Tom40

Yamano

Tanaka‐Yamano

Endo

2010

Journal of Biological Chemistry

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␤-Barrel membrane proteins in the mitochondrial outer membrane use the TOM40 complex to enter mitochondria and then the TOB/SAM complex to be assembled into the outer membrane. Tom7, a subunit of the TOM40 complex, regulates association of Mdm10 with the TOB complex. Here, we analyzed the role of Tom7 in assembly of ␤-barrel proteins, including Tom40, a central channel subunit of the TOM40 complex, and porin. Depletion of Tom7 decreased transient accumulation of Tom40 at the level of the TOB complex and retarded assembly of porin in vitro. On the other hand, overexpression of Tom7 resulted in enhanced accumulation of in vitro imported Tom40 in the TOB complex, yet it did not affect the in vitro assembly of porin. Site-specific photocrosslinking in vivo revealed that Tom7 directly interacts with Tom40 through its transmembrane segment and with Mdm10. These results collectively show that Tom7 recruits Mdm10, enhancing its association with the MMM1 complex, to regulate timing of the release of Tom40 from the TOB complex for subsequent assembly into the TOM40 complex.

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“…The blue native mobility of Mdm10 was not affected by the presence or absence of Mim1, in particular Mdm10 was not found in the 300-kDa SAM** form (Fig. 5A, lanes 7 and 8) (Mdm10 additionally forms a smaller complex not containing SAM subunits (37)). Thus Mdm10 is present in the 350-kDa SAM* complex independently of Mim1, excluding the first possibility.…”

Section: Figure 5 Association Of Mim1 With the Sam Complexmentioning

confidence: 98%

“…(iii) Mim1 is not a subunit of a large SAM complex but only required for its assembly or stability and thus in the absence of Mim1 the complex would partially dissociate leading to the SAM** form. We used antibodies against Mdm10 to decorate the known large SAM complex (36,37). The blue native mobility of Mdm10 was not affected by the presence or absence of Mim1, in particular Mdm10 was not found in the 300-kDa SAM** form (Fig.…”

Section: Figure 5 Association Of Mim1 With the Sam Complexmentioning

confidence: 99%

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Biogenesis of the Mitochondrial TOM Complex

Becker

Pfannschmidt

Guiard

et al. 2008

Journal of Biological Chemistry

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127

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The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming ␤-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane ␣-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM core components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the ␤-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex.The essential biochemical function of mitochondria depends on the uptake of cytosolic-synthesized precursor proteins. The vast majority of precursor proteins are imported by the preprotein translocase of the outer mitochondrial membrane (TOM 4 complex). Subsequently the precursor proteins are sorted to the different mitochondrial subcompartments, the outer and inner membranes, the intermembrane space and the matrix (1-7). The TOM complex is composed of seven different subunits. Tom40 forms the protein-conducting channel across the outer membrane (8 -10). The three receptors Tom20, Tom22, and Tom70 expose domains on the cytosolic side of the outer membrane, recognize the precursor proteins and direct them to the Tom40 channel (11). In addition, three small Tom proteins, Tom5, Tom6, and Tom7, are associated with the Tom40 core of the complex (12-14). Tom40 forms a transmembrane ␤-barrel, while all other Tom components are embedded in the membrane via a single transmembrane ␣-helix (9 -10, 15). The ␣-helical membrane anchor is localized in the C-terminal portion of Tom22 and the small Tom proteins and thus those proteins belong to the tail-anchored proteins (15-19). Tom20 and Tom70 are integrated into the outer membrane by an N-terminal ␣-helix, which together with flanking regions is important for both intracellular targeting and membrane anchoring, and thus these proteins are called signal-anchored proteins (20 -23).All Tom proteins are synthesized as precursor proteins on cytosolic ribosomes and imported into mitochondria. The import pathway of the precursor of t...

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Mitochondrial Protein Sorting

Cited by 91 publications

References 70 publications

The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?

The ubiquitous and ancient ER membrane protein complex (EMC): tether or not?

Tom7 Regulates Mdm10-mediated Assembly of the Mitochondrial Import Channel Protein Tom40

Biogenesis of the Mitochondrial TOM Complex

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