![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 18, Issue 2, 362-368, February 2007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*Laboratoire de Génétique Moléculaire, Centre National de la Recherche Scientifique-Ecole Normale Supérieure and Plateforme Transcriptome IFR36 Ecole Normale Supérieure, 75230 Paris Cedex 05, France; and Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461
Submitted September 15, 2006;
Revised November 3, 2006;
Accepted November 7, 2006
Monitoring Editor: Thomas Fox
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
; Rehling et al., 2004). Although a posttranslational mechanism for import is widely accepted, it may concern only a limited class of proteins. Indeed, it was demonstrated 30 years ago that a subclass of cytoplasmic polysomes is bound to the surface of mitochondria (Kellems et al., 1975). Subsequently, experiments in yeast and human cells have suggested a cotranslational import process for some mitochondrial proteins (Fujiki and Verner, 1993; Mukhopadhyay et al., 2004). The evolutionary history of mitochondria might elucidate this apparent discrepancy between post- and cotranslational import processes. Phylogenetic studies of the yeast mitochondrial proteome have demonstrated a composite origin. It is estimated that half or more of the genes that code for the modern mitochondrial proteome originated directly from the host nuclear genome, and the other half are of bacterial origin, a consequence of a massive transfer of genes from the endosymbiont to the host nuclear genome (Marcotte et al., 2000; Karlberg et al., 2000). This symbiotic situation required the development of protein translocation machineries (translocases) in the mitochondrial membranes (Herrmann, 2003). Possibly, the two classes of nuclear genes coding for mitochondrial products may have used the same mitochondrial import pathway. However, a recent genome-wide analysis (Marc et al., 2002) suggested a strong correlation between the bacterial origin of the genes and their locus specific translation on mitochondria-linked polysomes. An index called MLR (mitochondrial localization of mRNA) was derived from microarray analyses to classify (from 0 to 100) the mRNAs according to their cellular localization. A recent analysis of the outer membrane proteome (Zahedi et al., 2006) presented strong support for the MLR concept: it included both bona fide outer membrane proteins and precursors for many MLR proteins. This strongly suggests that the MLR proteins are translated next to mitochondria, although the reason for this remains obscure. In some cases, this phenomenon may favor the formation of nucleo-proteocomplexes in the vicinity of mitochondria, as for Msk1, the mitochondrial lysyl-tRNA synthetase, which guides the import of tRNALys toward mitochondria (Entelis et al., 2006). To describe the MLR phenomenon in more detail, we developed two highly sensitive methods to: 1) quantify, in vitro, the amount of mitochondrial-associated mRNA and 2) to visualize, in situ, the localization of some mRNA species. These approaches were applied to 112 nuclear mRNAs to establish a spatial map of the sites of translation of proteins involved in the assembly of seven mitochondrial complexes. We report a close link between core proteins and mitochondrially associated translation sites. The prokaryotic origin of most of these MLR proteins emphasizes the evolutionary stability of this phenomenon.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). Cells were grown at 30°C in galactose medium (1% bactopeptone, 1% yeast extract, 2% galactose) for overnight precultures and FISH experiments; for purification of mitochondria, cells were grown in the same medium plus 0.1% KH2PO4 and 0.12% (NH4)2SO4.
Quantitative PCR analysis of asymmetric mRNA localization. Schematically, mitochondrion-bound polysomes were purified as in Kellems et al. (1975), and RNA was extracted using the hot-phenol method. Aliquots of 50 ng of either total or mitochondria-associated mRNA were used for reverse transcription (RT), and the cDNA was purified using the Macherey-Nagel PCR extract kit. Serial dilutions (1/10, 1/50, 1/100) of cDNAs were subjected to real-time quantitative PCR with oligonucleotides specific for each ORF (Supplementary Table S1) and the Sybr Green PCR kit (QuantiTech).
For a reliable evaluation of the mRNA associated with mitochondria, various correction factors were used to account for the difficulties of the purification procedure. COX1 and COX2 mRNAs were used to normalize the data, assuming they have a 100% mitochondrial localization. ACT1 mRNA was used to assess the extent of contamination by nonmitochondrial fractions. The SD error by this approach varies from 0 to 5%, whereas previous microarray-based methods gave much less reproducible results (Marc et al., 2002). A detailed description of this approach (PCR programs and calculations) is available in Garcia et al. (2006) and in supplemental document S1.
FISH Analysis and In Situ mRNA Localization
The combined hybridization of three to five antisense oligonucleotides was used to enhance the visualization of each mRNA. Typically, each oligonucleotide was designed to contain 50–55 nucleotides with five aminoallyl thymidines and a coherent Tm value (±2°C for the set of oligonucleotide). After synthesis (Eurogentec, San Diego, CA) the oligonucleotides were directly labeled with CY3 or CY5 fluorochromes as previously described (Garcia et al., 2006). The probes used in this study are presented in Supplementary Table S2.
For in situ hybridization, yeast cells were grown to midlog phase and immediately fixed with a final concentration of 4% paraformaldehyde, spheroplasted with lyticase, adhered to poly-L-lysine–treated coverslips, and stored in 70% ethanol at –20°C. After overnight hybridization at 37°C, washing, and DAPI staining, coverslips were mounted with anti-fade solution and imaged on an Olympus BX61 upright microscope (Melville, NY) using a 100x 1.35 NA objective. For 3D sampling 41 images were acquired at a spacing of 200 nm in the Z-axis. ImageJ was used for image processing; several stacks can be combined using a maximum projection algorithm. We developed an extension ImageJ plug-in for calculating the distance from mRNA to mitochondrion objects (Jourdren and Garcia, unpublished results).
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
). A few studies (Diehn et al., 2000; Marc et al., 2002; de Jong et al., 2006) used DNA microarrays to establish a list of genes whose mRNA is preferentially translated on membrane-bound polysomes. Though providing an abundance of data, these studies were limited by substantial heterogeneity of the biochemical preparations and variations in the yield due to the purification procedure. For instance, the general conclusions of the DNA microarray analyses are probably sound concerning mitochondria-bound polysomes (Marc et al., 2002), but gene-specific data may be absent or inaccurate. Because it is possible to enrich mitochondrial fractions carrying associated cytoplasmic polysomes (Kellems et al., 1975), we developed a protocol with better discrimination. We used real-time quantitative RT-PCR with normalization and correction of the results to take into account the purification yield and contaminating factors (see Materials and Methods). Mitochondrial mRNAs were analyzed to assess the exact quantity of mitochondrial products in each extract as an internal control. The technical reproducibility of the procedure was verified by conducting three independent polysomal fractionations from different yeast cultures. mRNA from 112 genes was studied, and the percentage of each mRNA associated with mitochondria-bound polysomes was between 0 and 57% (Supplementary Table S1 and Supplementary Figure S1). Three classes of gene were distinguished. The first class includes the 56 genes that have between 0 and 3% of their mRNA linked to mitochondria; these mRNAs were considered to be translated on free cytoplasmic polysomes. The second class includes 50 genes for which 9–57% of their mRNA was linked to mitochondria: the corresponding proteins are probably produced in the vicinity of mitochondria, and they were considered to be MLR proteins (Figure 1). The third class, the intermediate group (4–6%), includes six genes that cannot be unambiguously classified to either class 1 or class 2. Classes 1 and 2 contain approximately the same number of genes, 56 and 50 respectively, as previously observed in a more global analysis (Marc et al., 2002). In contrast, data from the Saccharomyces Genome Database (Christie et al., 2004) and PSI-BLAST analysis (Altschul et al., 1997) indicate that 96% of the MLR genes, but only 8% of genes with nonlocalized mRNAs, are prokaryotic homologues (Figure 1 and Supplementary Table S1).
|
, 2003). The protocol we used here is adapted from Long et al. (1995, 1997) and can be used to compare, simultaneously, the spatial distribution of different mRNAs relative to each other or to the mitochondrion (see Materials and Methods). Mitochondria were unambiguously detected using probes recognizing mitochondrial ribosomal RNAs; this allowed simultaneous detection of mRNAs and mitochondria in a single step. Both haploid and diploid strains were examined, and because of their size, findings with diploid strains were easier to interpret. However, it was evident that in the results in the two genetic backgrounds were equivalent.
The findings of FISH experiments were entirely consistent with the results of the RT-PCR analyses. For all genes classified as MLR (>6% asymmetrical localization of the mRNA), as exemplified by ATP1, ATP2, and ATP3 (Figure 2), the FISH signal localized to punctuate structures that aligned with mitochondria. Conversely ATP16 (0% by RT-PCR) had its mRNA isotropically dispersed in the cell with no apparent association with mitochondria (Figure 2 and Supplementary Figure 2S for 3D quantification analysis). Almost all MLR genes seem to be of prokaryotic origin (Figure 1), although a few, including ATP4 and TIM50, have no prokaryotic homolog (Saccharomyces Genome Database; Christie et al., 2004); FISH analyses fully confirmed that the corresponding mRNAs of these two atypical cases were translated adjacent to mitochondria (Figure 2). This is also consistent with the detection of precursor forms of these proteins in the outer mitochondrial membrane proteome (Zahedi et al., 2006).
|
The Krebs TCA cycle enzymes are believed to be highly organized in supramolecular complexes (Velot et al., 1997) connected to the other supermacromolecular complex, succinate:quinone oxidoreductase (SQR, Complex II; Horsefield et al., 2004). All the 16 proteins comprising these two complexes are unambiguously MLR proteins. This applies even to Tcm62, which is considered to be a putative protein chaperone required for complex II assembly.
The ATP synthase complex (RCC5) is composed of proteins of diverse origins, and its structure and biosynthesis are well documented (Ackerman and Tzagoloff, 2005). Three MLR proteins, ATP1 (subunit 
), ATP2 (subunit 
), and ATP3 (subunit 
) are components of the F1 subunit, and three other MLR proteins, ATP4 (subunit b), ATP5 (OSCP), and ATP10 (essential chaperone for F0) are essential for F0 subunit construction. Genetic and biochemical experiments have demonstrated that the , , , b, and OSCP subunits are the basic elements of the F1 and F0 complexes (see Ackerman and Tzagoloff, 2005 for a review). The case of ATP10 is less straightforward. There is genetic interaction between ATP10 and ATP6, the mitochondrial gene for subunit a, suggesting that Atp10 may act as a subunit a-chaperone at early stages of F0 assembly (Tzagoloff et al., 2004). Interestingly, the five basic subunits of the ATP synthase (, , , b, and OSCP) are all translated in the vicinity of mitochondria. Conversely, none of the 13 accessory genes required for yeast ATP synthase biogenesis (Ackerman and Tzagoloff, 2005) are MLR proteins. Thus, translation near the mitochondrion appears to be a characteristic of the early nucleation process of the core enzyme.
The case of the COX complex (RC4) deserves a special mention: none of the mRNAs of nuclear-encoded subunits were translated in the vicinity of mitochondria. However, Shy1, Sco1, Oxa1, Cox10, Cox11, and Cox15 (Figure 1), important for the assembly of this complex (Nijtmans et al., 2001; Szyrach et al., 2003), are undoubtedly MLR proteins.
The bc1 complex (RC3) is a complex of tripartite origin: the apocytochrome b is always encoded in the mitochondrial genome, and some of its nuclear-encoded subunits are MLR proteins, whereas others are translated on free cytoplasmic polysomes. The core proteins of the complex—Cor1, Cor2, Rip1 and Cyt1—clearly belong to the MLR protein class and they are unambiguously of a prokaryotic origin. Cbp3, like Atp10 for complex V, is a chaperone essential for complex III biosynthesis (Kronekova and Rodel, 2005), suggesting that there is in all cases at least one chaperone associated with the assembly of these core proteins. Thus, the bc1 complex shares various similarities with the ATP synthase complex.
The TOM and TIM complexes differ from the previous examples from an evolutionary point of view. This import machinery emerged as a consequence of the endosymbiosis. The synthesis of mitochondrial proteins in the cytosol required the development of protein translocation systems to ensure appropriate localization. Consequently, few of these translocase components have obvious bacterial homologues and most are of eukaryotic origin. Systematic analysis of the MLR subunits composing these complexes provided an interesting observation. At least one of the components of each subcomplex of the translocase machinery (Koehler, 2004) is unambiguously an MLR protein (SAM = SAM50, TOM = TOM70, TIM22 = TIM54, Export = OXA1). This is consistent with the suggestion that the ability of mitochondria to bind mRNAs for the genes coding for targeted proteins would alleviate the problem of targeting the prokaryotic proteins (Herrmann, 2003). As in the respiratory complexes, most of the MLR proteins are critical to the biogenesis of the complex. SAM50, for instance, is required for viability and probably forms the core of the SAM complex (Paschen et al., 2003; Kozjak et al., 2003; Pfanner et al., 2004). The TOM translocase is composed of seven proteins and the MLR proteins Tom70 and Tom40 are crucial to the properties of the complex. Tim50, an essential protein of the complex TIM23, has no prokaryotic homolog but its MLR localization and the FISH analyses identify it as an MLR protein. This might be an example of a protein becoming MLR through acquisition of specific targeting signals. Finally, Mia40, a recently discovered protein (Chacinska et al., 2004), is a central component of the protein import and assembly machinery. Mia40 is required for the assembly of small proteins of the intramembrane space (Rissler et al., 2005). The identification of Mia40 as an MLR protein (of prokaryotic origin) is entirely consistent with its importance in the construction of this mitochondrial domain.
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
), whereas 53 of the 62 non-MLR proteins translated on free cytoplasmic polysomes are of eukaryotic origin (no homology found in the available prokaryotic sequences). This suggests that a strong selective pressure has maintained a mitochondria-linked translation mechanism for MLR proteins. This apparently ancestral process raises the following various interesting considerations.
MLR Proteins and Protein-Translocation Pathways
A recent survey (Herrmann and Hell, 2005) of the mechanisms by which proteins of the mitochondrial intermembrane space (IMS) are transported from the cytosol has revealed three main classes. These classes differ in the energy sources used to drive the translocation reactions. We examined the MLR values of most of these proteins (Figure 3) and found that class I proteins are exclusively MLR proteins, whereas the class II and III proteins are non-MLR proteins. The well-characterized class I proteins have bipartite presequences composed of matrix-targeting N-terminal sequences followed by hydrophobic sorting domains. Unlike class II or III proteins, class I protein importation into IMS is TIM23 complex dependent, and consequently class I (MLR) protein importation relies on a physical chain of interactions between TOM and TIM23 complexes. Thus, class I protein import may require a tight connection between cytoplasmically localized translation and sites of outer–inner membrane association.
|
). Subunits (ATP1), (ATP2), and (ATP3) of the F1 subunit and subunit b (ATP4), OSCP (ATP5), and the essential chaperone Atp10 (ATP10) of the F0 subunit are all essential for the early steps of ATP synthase biogenesis, and are all MLR proteins. MLR proteins appear to be critical early during biogenesis of most of the complexes described above. This strongly suggests that the MLR-specific translation sites (the punctate structures in Figure 2) might also be the sites of initiation of the early steps of complex construction. Systematic relative localization analysis of these translation sites may further elucidate the space and time-controlled biogenesis of mitochondrial complexes.
MLR Protein Translation and Membrane Contact Sites
We can suggest a model (Figure 4) in which MLR proteins are translated at specific sites near the outer mitochondrial membrane. This is reminiscent of the mitochondrial mRNA translation process: for some mRNAs, including those of the COX1, COX2, and CYTb genes, specific translation sites at the inner mitochondrial membrane have been demonstrated. This site-specific translation depends on the mRNA associating with identified protein complexes (Naithani et al., 2003; Krause et al., 2004). The protein Oxa1 establishes, in some cases, a link with ribosomes to ensure cotranslational insertion of the nascent mitochondrial-encoded polypeptides into the membrane (Szyrach et al., 2003). Possibly, mitochondrial genes translocated to the nucleus after the symbiotic event have continued to use the same translation process. This membrane-controlled production might have facilitated the early steps of symbiosis when primitive mitochondrial genes became nuclear at a time when the mitochondrial import machineries did not exist.
|
). Also the fact that, in the intermembrane space, MLR proteins are imported via a chain of physical contacts between the two membranes gives further credence to this idea (see above and Figure 3). The improved FISH methodology presented in this work should allow us to address this issue experimentally.
MLR Proteins and Cellular Compartments
There may be damaging effects of site-specific translation of MLR proteins. The location of many mRNAs close to mitochondria may be deleterious if reactive oxygen species (ROS) production alters these molecules. For example, in Alzheimer's disease, it was observed that ROS production in the mitochondrial environment may cause excessive mRNA oxidation (Shan et al., 2003). Peri-mitochondrial translation might thus promote exposure of the mRNAs concerned to free radicals, with subsequent aggregation of the translation products (Swerdlow and Khan, 2004). However, a healthy wild-type cell is likely to minimize this possibility by a time-dependent compartmentalization process that disconnects mitochondria biogenesis and ROS production (Tu et al., 2005). It would be interesting to study how MLR protein production is regulated temporally.
|
ACKNOWLEDGMENTS |
|---|
|
Footnotes |
|---|
The online version of this contains supplemental material at MBC Online (http://www.molbiolcell.org). 
This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-09-0827) on November 15, 2006.
Address correspondence to: Claude Jacq (jacq{at}biologie.ens.fr)
Abbreviations used: MLR, mitochondria-localized mRNA.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W., Lipman, D. J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25, 3389–3402.
Chacinska, A., Pfannschmidt, S., Wiedemann, N., Kozjak, V., Sanjuan Szklarz, L. K., Schulze-Specking, A., Truscott, K. N., Guiard, B., Meisinger, C., Pfanner, N. (2004). Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J 23, 3735–3746.[CrossRef][Medline]
Christie, K. R., et al. (2004). Saccharomyces Genome Database (SGD) provides tools to identify and analyze sequences from Saccharomyces cerevisiae and related sequences from other organisms. Nucleic Acids Res 32, D311–D314.
Darzacq, X., Powrie, E., Gu, W., Singer, R. H., Zenklusen, D. (2003). RNA asymmetric distribution and daughter/mother differentiation in yeast. Curr. Opin. Microbiol 6, 614–620.[CrossRef][Medline]
de Jong, M., van Breukelen, B., Wittink, F. R., Menke, F. L., Weisbeek, P. J., Van den Ackerveken, G. (2006). Membrane-associated transcripts in Arabidopsis; their isolation and characterization by DNA microarray analysis and bioinformatics. Plant J 46, 708–721.[CrossRef][Medline]
Diehn, M., Eisen, M. B., Botstein, D., Brown, P. O. (2000). Large-scale identification of secreted and membrane-associated gene products using DNA microarrays. Nat. Genet 25, 58–62.[CrossRef][Medline]
Entelis, N., Brandina, I., Kamenski, P., Krasheninnikov, I. A., Martin, R. P., Tarassov, I. (2006). A glycolytic enzyme, enolase, is recruited as a cofactor of tRNA targeting toward mitochondria in Saccharomyces cerevisiae. Genes Dev 20, 1609–1620.
Femino, A. M., Fay, F. S., Fogarty, K., Singer, R. H. (1998). Visualization of single RNA transcripts in situ. Science 280, 585–590.
Femino, A. M., Fogarty, K., Lifshitz, L. M., Carrington, W., Singer, R. H. (2003). Visualization of single molecules of mRNA in situ. Methods Enzymol 361, 245–304.[Medline]
Fujiki, M. and Verner, K. (1993). Coupling of cytosolic protein synthesis and mitochondrial protein import in yeast. Evidence for cotranslational import in vivo. J. Biol. Chem 268, 1914–1920.
Garcia, M., Darzacq, X., Devaux, F., Singer, R. H., Jacq, C. (2006). In: Methods in Molecular Biology: Mitochondria, ed. D. Leister and J. M. Herrmann. Totowa, NJ: Humana Press, Vol. 372, 505–527.
Herrmann, J. M. (2003). Converting bacteria to organelles: evolution of mitochondrial protein sorting. Trends Microbiol 11, 74–79.[CrossRef][Medline]
Herrmann, J. M. and Hell, K. (2005). Chopped, trapped or tacked—protein translocation into the IMS of mitochondria. Trends Biochem. Sci 30, 205–211.[CrossRef][Medline]
Horsefield, R., Iwata, S., Byrne, B. (2004). Complex II from a structural perspective. Curr. Protein Pept. Sci 5, 107–118.[CrossRef][Medline]
Karlberg, O., Canback, B., Kurland, C. G., Andersson, S. G. (2000). The dual origin of the yeast mitochondrial proteome. Yeast 17, 170–187.[CrossRef][Medline]
Kellems, R. E., Allison, V. F., Butow, R. A. (1975). Cytoplasmic type 80S ribosomes associated with yeast mitochondria. IV. Attachment of ribosomes to the outer membrane of isolated mitochondria. J. Cell Biol 65, 1–14.
Koehler, C. M. (2004). New developments in mitochondrial assembly. Annu. Rev. Cell Dev. Biol 20, 309–335.[CrossRef][Medline]
Kozjak, V., Wiedemann, N., Milenkovic, D., Lohaus, C., Meyer, H. E., Guiard, B., Meisinger, C., Pfanner, N. (2003). An essential role of Sam50 in the protein sorting and assembly machinery of the mitochondrial outer membrane. J. Biol. Chem 278, 48520–48523.
Krause, K., Lopes de Souza, R., Roberts, D. G., Dieckmann, C. L. (2004). The mitochondrial message-specific mRNA protectors Cbp1 and Pet309 are associated in a high-molecular weight complex. Mol. Biol. Cell 15, 2674–2683.
Kronekova, Z. and Rodel, G. (2005). Organization of assembly factors Cbp3p and Cbp4p and their effect on bc(1) complex assembly in Saccharomyces cerevisiae. Curr. Genet 47, 203–212.[CrossRef][Medline]
Long, R. M., Elliott, D. J., Stutz, F., Rosbash, M., Singer, R. H. (1995). Spatial consequences of defective processing of specific yeast mRNAs revealed by fluorescent in situ hybridization. RNA 1, 1071–1078.[Abstract]
Long, R. M., Singer, R. H., Meng, X., Gonzalez, I., Nasmyth, K., Jansen, R. P. (1997). Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. Science 277, 383–387.
Marc, P., Margeot, A., Devaux, F., Blugeon, C., Corral-Debrinski, M., Jacq, C. (2002). Genome-wide analysis of mRNAs targeted to yeast mitochondria. EMBO Rep 3, 159–164.[CrossRef][Medline]
Marcotte, E. M., Xenarios, I., van Der Bliek, A. M., Eisenberg, D. (2000). Localizing proteins in the cell from their phylogenetic profiles. Proc. Natl. Acad. Sci. USA 97, 12115–12120.
Mukhopadhyay, A., Ni, L., Weiner, H. (2004). A co-translational model to explain the in vivo import of proteins into HeLa cell mitochondria. Biochem. J 382, 385–392.[CrossRef][Medline]
Naithani, S., Saracco, S. A., Butler, C. A., Fox, T. D. (2003). Interactions among COX1, COX2, and COX3 mRNA-specific translational activator proteins on the inner surface of the mitochondrial inner membrane of Saccharomyces cerevisiae. Mol. Biol. Cell 14, 324–333.
Nijtmans, L. G., Artal Sanz, M., Bucko, M., Farhoud, M. H., Feenstra, M., Hakkaart, G. A., Zeviani, M., Grivell, L. A. (2001). Shy1p occurs in a high molecular weight complex and is required for efficient assembly of cytochrome c oxidase in yeast. FEBS Lett 498, 46–51.[CrossRef][Medline]
Paschen, S. A., Waizenegger, T., Stan, T., Preuss, M., Cyrklaff, M., Hell, K., Rapaport, D., Neupert, W. (2003). Evolutionary conservation of biogenesis of beta-barrel membrane proteins. Nature 426, 862–866.[CrossRef][Medline]
Pfanner, N., Wiedemann, N., Meisinger, C., Lithgow, T. (2004). Assembling the mitochondrial outer membrane. Nat. Struct. Mol. Biol 11, 1044–1048.[CrossRef][Medline]
Rehling, P., Brandner, K., Pfanner, N. (2004). Mitochondrial import and the twin-pore translocase. Nat. Rev. Mol. Cell Biol 5, 519–530.[CrossRef][Medline]
Rissler, M., Wiedemann, N., Pfannschmidt, S., Gabriel, K., Guiard, B., Pfanner, N., Chacinska, A. (2005). The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins. J. Mol. Biol 353, 485–492.[CrossRef][Medline]
Saint-Georges, Y., Bonnefoy, N., di Rago, J. P., Chiron, S., Dujardin, G. (2002). A pathogenic cytochrome b mutation reveals new interactions between subunits of the mitochondrial bc1 complex. J. Biol. Chem 277, 49397–49402.
Shan, X., Tashiro, H., Lin, C. L. (2003). The identification and characterization of oxidized RNAs in Alzheimer's disease. J. Neurosci 23, 4913–4921.
Swerdlow, R. H. and Khan, S. M. (2004). A "mitochondrial cascade hypothesis" for sporadic Alzheimer's disease. Med. Hypotheses 63, 8–20.[CrossRef][Medline]
Szyrach, G., Ott, M., Bonnefoy, N., Neupert, W., Herrmann, J. M. (2003). Ribosome binding to the Oxa1 complex facilitates co-translational protein insertion in mitochondria. EMBO J 22, 6448–6457.[CrossRef][Medline]
Tu, B. P., Kudlicki, A., Rowicka, M., McKnight, S. L. (2005). Logic of the yeast metabolic cycle: temporal compartmentalization of cellular processes. Science 310, 1152–1158.
Tzagoloff, A., Barrientos, A., Neupert, W., Herrmann, J. M. (2004). Atp10p assists assembly of Atp6p into the F0 unit of the yeast mitochondrial ATPase. J. Biol. Chem 279, 19775–19780.
Velot, C., Mixon, M. B., Teige, M., Srere, P. A. (1997). Model of a quinary structure between Krebs TCA cycle enzymes: a model for the metabolon. Biochemistry 36, 14271–14276.[CrossRef][Medline]
Zahedi, R. P., Sickmann, A., Boehm, A. M., Winkler, C., Zufall, N., Schonfisch, B., Guiard, B., Pfanner, N., Meisinger, C. (2006). Proteomic analysis of the yeast mitochondrial outer membrane reveals accumulation of a subclass of preproteins. Mol. Biol. Cell 17, 1436–1450.
This article has been cited by other articles:
|
|
 |
|
  E. Eliyahu, L. Pnueli, D. Melamed, T. Scherrer, A. P. Gerber, O. Pines, D. Rapaport, and Y. Arava Tom20 Mediates Localization of mRNAs to Mitochondria in a Translation-Dependent Manner Mol. Cell. Biol., January 1, 2010; 30(1): 284 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lee, G. Kramer, D. E. Graham, and D. R. Appling Yeast Mitochondrial Initiator tRNA Is Methylated at Guanosine 37 by the Trm5-encoded tRNA (Guanine-N1-)-methyltransferase J. Biol. Chem., September 21, 2007; 282(38): 27744 - 27753. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
