Why genes persist in organelle genomes
© BioMed Central Ltd 2005
Published: 29 April 2005
Mitochondria and plastids (including chloroplasts) have a small but vital genetic coding capacity, but what are the properties of some genes that dictate that they must remain encoded in organelles?
The sequencing of both organelle and nuclear genomes from phylogenetically diverse species will help us to infer how these genomes have evolved and the forces that have shaped them. Recent findings of high rates of transfer of organelle DNA to the nucleus , and of high rates of functional gene transfer from organelles to the nucleus [2–5], demonstrate that the endosymbiotic origin of organelles was a major determinant in defining eukaryotic nuclear genomes and was probably a defining event for the formation of the eukaryotic cell [1, 6]. Clearly there is an evolutionary pressure to centralize genetic information in the nucleus, but the forces behind this transfer are not obvious. Muller's ratchet - the unidirectional process of building up mutations in an asexually reproducing population - is one commonly suggested hypothesis to account for this centralization, but is limited in its ability to explain more 'recent' gene transfer events (reviewed in ). But despite a wealth of information, it is still not clear from genome sequencing why some genes remain encoded in organelles such as mitochondria and chloroplasts.
Too hot to handle - have organellar genes been 'trapped'?
The idea that some genes have been trapped in organellar genomes stems largely from the idea that the proteins encoded by these genes are difficult to transport back to the organelle for assembly when synthesized in the cytosol. Intrinsic to this idea is that there has been a hierarchical loss of organellar genes, whereby those that were first to be successfully relocated were those encoding proteins that are easiest to transport back, while those that were last to be transferred encode proteins that are difficult to transport back. Many bacterial proteins have or are predicted to have mitochondrial targeting properties, or can be targeted to mitochondria without the acquisition of a targeting presequence, and these are predicted to be the first organellar genes to be successfully relocated to the nucleus [10, 11]. As there seem to be no limitations on the transfer of genetic material, organellar gene loss should, according to this theory, have continued until the cell solved the targeting and assembly problems for all proteins, and organellar genomes would then no longer exist . This may yet occur in plants, where transfer of organellar genes to the nucleus continues to erode the organelle genomes .
Following the original hydrophobicity hypothesis , several studies have shown that targeting to mitochondria and the endoplasmic reticulum are competing pathways and that subcellular location is determined by a combination of the length of the transmembrane region, the degree of hydrophobicity and the number of positive residues flanking the transmembrane region [18, 19]. Specifically, it was concluded that moderate transmembrane region length and charge distribution resulted in mitochondrial targeting for some proteins, whereas increasing the length of the transmembrane region resulted in mis-localization to other membrane systems [20, 21]. Although these proteins were not organelle-encoded, the findings demonstrate that hydrophobic transmembrane regions can cause mis-targeting of cytosolically synthesized proteins.
Evidence that organelles are unable to import certain hydrophobic proteins has also accumulated since the initial observations that there was a limit on the number of transmembrane regions that could be imported . Direct experimental evidence indicates that a reduction in hydrophobicity was essential for the rare transfer event that occurred for the cytochrome c oxidase subunit 2 (Cox2) gene in legumes . Also, the other rare gene transfer events of Cox2, Cox3 and ATP6 from the mitochondrion in green algae have been accompanied by a reduction in hydrophobicity of the encoded protein [23–25]. These events highlight the fact that there are hydrophobicity limits on import, and that many mitochondrially encoded proteins lie naturally outside this limit. But they also indicate that in those organisms for which the location of the gene has not been 'frozen' by a change in genetic code, organellar genomes will continue to be eroded.
Another observation that suggests that gene location is affected by hydrophobicity is the finding that cytochrome f and subunit IV of the cytochrome bf complex of Euglena gracilis are encoded in the nucleus . Euglena is somewhat unusual as it has three chloroplast-envelope membranes because an additional endosymbiosis has taken place and thus the outer envelope membrane - the perichloroplast membrane - is closely related to the endoplasmic membrane. As well as the decrease in hydrophobicity of the cytochrome f and subunit IV polypeptides in relation to their chloroplast-encoded counterparts, it is tempting to speculate that this transfer was only feasible because of the additional outer membrane, as proteins destined for the chloroplast in Euglena are first targeted co-translationally to the endoplasmic reticulum and subsequently sorted to the chloroplast (see below) .
The solutions that nature has found for overcoming the hydrophobicity problem associated with relocating some genes have been both original and instructive. Similar efforts by researchers to express organellar genes allotopically have proven difficult and also give credit to the hydrophobicity hypothesis. Although the coding location could be experimentally moved from the mitochondrion to the nucleus for ATP6 and ATP8 [28, 29], this could not be achieved for apocytochrome b or ND4 . Additionally, overexpression resulted in depolarization of the mitochondrial membrane potential. Thus these proteins seem to have a toxic effect on cells when expressed in the cytosol, and this may be linked to their hydrophobic nature .
Hard-wired - have organellar genes been 'preferentially maintained'?
The preferential 'maintenance' of a core set of organellar genes is encompassed by the CORR theory (co-location for redox regulation; see Box 1), which was first proposed in 1992 [30, 31]. This hypothesis proposes that there is a direct link between coding location and regulation, either transcriptional or post-transcriptional, which gives a fitness advantage compared with nuclear-encoded genes. In this way, expression of a gene within the organelle gives an advantage, thus preventing transfer of the gene to the nucleus. An example often quoted to support the hypothesis is that if more subunits of a protein complex are needed in a particular chloroplast, for example the DI subunit of photosystem II, which might be required because of photo-oxidative damage, it is more efficient to have the gene encoded within the organelle, as nuclear encoding would mean that the protein would be sent even to those chloroplasts that did not require this subunit . Although rich in predictions, there is no direct experimental evidence for CORR (for mitochondria) , in contrast to several experimental investigations that support the validity of the hydrophobicity hypothesis [5, 16–26, 28, 29].
The flaws of each hypothesis
On the surface, the hydrophobicity hypothesis does not appear to adequately explain the retention of all organelle-encoded genes. Notable flaws are, firstly, that not all protein-coding genes encoded in organelles encode hydrophobic proteins, the most obvious example being the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco-LSU) in chloroplasts; and secondly, both mitochondria and chloroplast already import hydrophobic proteins. The mitochondrial carrier family and the light-harvesting protein of the light-harvesting chlorophyll-protein complex are cited examples for mitochondria and chloroplasts, respectively.
Similarly, the CORR hypothesis also has some deficiencies. Firstly, redox control has as yet been demonstrated for only a handful of plastid-encoded genes. Secondly, the expression of many nuclear-encoded mitochondrial and chloroplast proteins is under redox control and yet these proteins are not organelle-encoded [33, 34]; thus, why only some redox-controlled genes must be organelle-encoded is not explained by CORR. And thirdly, even for the redox-regulated components encoded by chloroplasts, the products are functional only when combined with additional nuclear-encoded subunits; thus, being organelle-encoded does not offer any immediate advantage in terms of protein function.
Thus it might be possible that there are a variety of reasons why genes are organellar and the reason for each gene might differ, or even be a combination of a number of different factors. It is worth examining the exceptions to each hypothesis to see whether there is evidence to validate or invalidate the objection. Also, there is a need to question how being chloroplast-encoded and under redox control is an advantage in evolutionary terms.
Exceptions to the rule
The hydrophobicity hypothesis centers on the problem of targeting and importing a protein following its synthesis in the cytosol. Although hydrophobic proteins clearly present targeting problems, many organellar genes do not encode hydrophobic proteins. If we look at Rubisco-LSU, as it is the obvious and cited counterexample to the hydrophobicity hypothesis, can it be synthesized in the cytosol and imported to produce a functional protein in chloroplasts? The answer is yes, as this has been successfully achieved in some dinoflagellates . In other plants where Rubisco-LSU is normally plastid-encoded the reported attempts to express the gene allotopically have been successful qualitatively but not quantitatively. Although it is possible to express and import the protein, only a small proportion of the wild-type activity can be achieved . One reason for this failure might relate to the assembly of the complex. As the holoenzyme of Rubisco is the most abundant protein in a cell, efficient assembly is critical, and specific chaperone systems are involved in this process (for review, see ). Thus, although it is possible to import the protein, the limitations of assembly - that is, reduced assembly efficiency - may reduce fitness and thus successful gene transfer. An unfolded protein response, a stress-induced pathway, has been described for mitochondria and thus, in addition to the fact that inefficient assembly may reduce fitness, unfolded or unassembled proteins may be degraded and/or may induce stress pathways, as has been demonstrated in mitochondria [36, 37]. It should be noted that as the small subunit of Rubisco is nuclear-encoded, the reason for the failure to express Rubisco-LSU adequately from a nuclear location is unlikely to be due to a gene dosage effect of plastid genome versus nuclear genome.
This assembly concept could be extended further to explain the organellar coding location of other proteins that are not encompassed by the hydrophobicity hypothesis. One common feature of almost all organelle-encoded genes is that the products are assembled into multisubunit complexes that contain at least one other protein - for example the Rubisco holoenzyme - but usually many others, as is evident for the electron-carrying components of the photosynthetic and respiratory chains. Studies on how such complexes assemble indicate that there are ordered sequential assembly pathways. The order of assembly is critical to producing a functional complex, and importantly organelles have specific protease and chaperone systems for degrading proteins that have not assembled correctly [38, 39].
The extensively studied photosystem II from chloroplasts indicates "a hierarchy in the protein components that allows a stepwise building of the complex" . An excellent example is the DI protein, which is encoded by the chloroplast gene psbA. This protein is inserted into the thylakoid membrane in a co-translational manner with the aid of the chloroplast signal-recognition particle, and requires the presence of several other subunits of photosystem II [40, 41]. Studies of the unicellular green alga Chlamydomonas reinhardtii indicate that specific sequences in the 5'-untranslated region of the mRNA bind specific proteins that might define thylakoid membrane targeting . Allotopic expression of genetically altered psbA resistant to herbicide demonstrated that the protein product could be imported into chloroplasts but plants were still sensitive to herbicide (albeit less than wild-type plants) , possibly as a result of ineffective or inefficient assembly of the cytosolically synthesized protein. This example indicates that assembly may define an organelle-encoded location. An excellent review containing more details of this process is available .
The second apparent 'flaw' in the hydrophobicity hypothesis is that both mitochondria and chloroplast import many hydrophobic proteins. Why then should some hydrophobic proteins be resistant to this process? The answer may lie in the protein itself; many nuclear-encoded mitochondrial proteins are imported across the organellar membranes to the matrix, and then rerouted via conserved sorting pathways. This import pathway requires that all but the last transmembrane stretch must pass through the import machinery. If, however, a transmembrane stretch is recognized as a 'stop-transfer' sequence, the import process stops , the offending stretch of amino acids is moved laterally into the membrane, and the protein is unable to fold to its active conformation . Clearly, all nuclear-encoded organellar proteins have evolved so that their transmembrane stretches do not resemble stop-transfer sequences, enabling polytopic proteins to be easily imported and assembled. Thus it is the subtle signals contained in a transmembrane stretch that can prevent import, something we are not yet able to predict from gene sequence alone.
The often-cited examples of mitochondria and chloroplasts importing hydrophobic proteins do not contradict the principle that assembly can define organelle-coding location. Members of the mitochondrial carrier family, present in the inner membrane, may be hydrophobic but function in homodimeric complexes; thus there is no sequential assembly required . The hydrophobic light-harvesting chlorophyll proteins were derived from simpler forms in cyanobacteria that are single-membrane-spanning [47, 48]. These two sets of proteins represent 'eukaryotic' proteins and thus import and assembly pathways were invented de novo by eukaryotic cells. But, when multisubunit protein complexes were derived from the endosymbiotic ancestor, the assembly pathways were dictated.
One, two or more reasons not to move?
As outlined above, there is compelling experimental evidence that the targeting and import of some proteins might be the major determinant for their organelle-coding location. But not all organelle-encoded proteins pose targeting and import problems, and it is becoming increasing clear that assembly should be added to the list of difficulties. We therefore feel that the term 'importability' better encompasses the difficulties experienced by some proteins when expressed in the cytosol, and therefore the retention of organellar genomes. The importability concept does not ignore the observations of the CORR hypothesis: rather, the elegant redox regulation of some chloroplast-encoded genes  may be a mechanism for ensuring that these organelle-encoded subunits are synthesized in the correct sequential manner, so as to ensure correct assembly. Redox regulation may have specialized to a stage at which it facilitates the ordered assembly of multisubunit complexes and may now represent a barrier to gene relocation.
The importability hypothesis also encompasses the proposal that some products may be toxic if synthesized in a cytosolic location, as has been demonstrated for the apocytochrome b and ND4 proteins . An important point to note is that even if, under experimental conditions, allotopic expression of some organelle genes can be achieved and can rescue mutant phenotypes, in evolutionary terms it is the efficiency of import and assembly that can be a selective factor. Thus, reducing the growth rate by achieving allotopic expression may reduce fitness and result in an organellar location for a gene even though a nuclear location can be achieved in the laboratory.
Importability may not be sufficient to explain an organellar coding location for all genes in all organisms. There might be alternative reason(s) why some genes are retained in organelles. The evolution of organellar and nuclear genomes must be a complementary process in cells. Effective cross-talk takes place between nuclear and organellar genomes to coordinate function, as is evident with retrograde regulation for nuclear-encoded genes for mitochondrial and chloroplast proteins [49–51]. There is also evidence for an additional form of regulation, termed intergenomic communication [52, 53]; this is based on the physical presence and expression of a gene within an organelle genome independent of the function of the encoded protein . Furthermore, it appears that mutations in the mitochondrial genome in yeast increase the rate of nuclear mutation . Mutations in mitochondrial genomes cause defects or alterations in development in mammalian and plant systems [56, 57]. Thus, perhaps an additional reason that genes are encoded in organelles is that some genes must be encoded there in order for expression of organelle and nuclear genomes to be coordinated. Genes encoding protein products that present additional barriers for successful gene transfer will also most often be observed in organelle genomes. With all the genome information that is now available, care needs to be taken to look at genomes rather than focusing solely on individual genes. This approach may yield insights that would not be possible with single-gene analysis and may provide more inclusive hypotheses for explaining organelle genome maintenance.
This work is supported by grants from the Australian Research Council to J.W. D.O.D. is the recipient of an EMBO long-term fellowship.
- Timmis JN, Ayliffe MA, Huang CY, Martin W: Endosymbiotic gene transfer: organelle genomes forge eukaryotic chromosomes. Nat Rev Genet. 2004, 5: 123-135. 10.1038/nrg1271.PubMedView ArticleGoogle Scholar
- Martin W, Stoebe B, Goremykin V, Hapsmann S, Hasegawa M, Kowallik KV: Gene transfer to the nucleus and the evolution of chloroplasts. Nature. 1998, 393: 162-165. 10.1038/30234.PubMedView ArticleGoogle Scholar
- Adams KL, Daley DO, Qiu YL, Whelan J, Palmer JD: Repeated, recent and diverse transfers of a mitochondrial gene to the nucleus in flowering plants. Nature. 2000, 408: 354-357. 10.1038/35042567.PubMedView ArticleGoogle Scholar
- Adams KL, Qiu YL, Stoutemyer M, Palmer JD: Punctuated evolution of mitochondrial gene content: high and variable rates of mitochondrial gene loss and transfer to the nucleus during angiosperm evolution. Proc Natl Acad Sci USA. 2002, 99: 9905-9912. 10.1073/pnas.042694899.PubMedPubMed CentralView ArticleGoogle Scholar
- Adams KL, Palmer JD: Evolution of mitochondrial gene content: gene loss and transfer to the nucleus. Mol Phylogenet Evol. 2003, 29: 380-395. 10.1016/S1055-7903(03)00194-5.PubMedView ArticleGoogle Scholar
- Martin W, Muller M: The hydrogen hypothesis for the first eukaryote. Nature. 1998, 392: 37-41. 10.1038/32096.PubMedView ArticleGoogle Scholar
- Sickmann A, Reinders J, Wagner Y, Joppich C, Zahedi R, Meyer HE, Schonfisch B, Perschil I, Chacinska A, Guiard B, et al: The proteome of Saccharomyces cerevisiae mitochondria. Proc Natl Acad Sci USA. 2003, 100: 13207-13212. 10.1073/pnas.2135385100.PubMedPubMed CentralView ArticleGoogle Scholar
- Kleffmann T, Russenberger D, von Zychlinski A, Christopher W, Sjolander K, Gruissem W, Baginsky S: The Arabidopsis thaliana chloroplast proteome reveals pathway abundance and novel protein functions. Curr Biol. 2004, 14: 354-362. 10.1016/j.cub.2004.02.039.PubMedView ArticleGoogle Scholar
- Heazlewood JL, Tonti-Filippini JS, Gout AM, Day DA, Whelan J, Millar AH: Experimental analysis of the Arabidopsis mitochondrial proteome highlights signaling and regulatory components, provides assessment of targeting prediction programs, and indicates plant-specific mitochondrial proteins. Plant Cell. 2004, 16: 241-256. 10.1105/tpc.016055.PubMedPubMed CentralView ArticleGoogle Scholar
- Baker A, Schatz G: Sequences from a prokaryotic genome or the mouse dihydrofolate reductase gene can restore the import of a truncated precursor protein into yeast mitochondria. Proc Natl Acad Sci USA. 1987, 84: 3117-3121.PubMedPubMed CentralView ArticleGoogle Scholar
- Lucattini R, Likic VA, Lithgow T: Bacterial proteins predisposed for targeting to mitochondria. Mol Biol Evol. 2004, 21: 652-658. 10.1093/molbev/msh058.PubMedView ArticleGoogle Scholar
- Palmer JD: Organelle genomes: going, going, gone!. Science. 1997, 275: 790-791. 10.1126/science.275.5301.790.PubMedView ArticleGoogle Scholar
- Boore JL: Animal mitochondrial genomes. Nucleic Acids Res. 1999, 27: 1767-1780. 10.1093/nar/27.8.1767.PubMedPubMed CentralView ArticleGoogle Scholar
- Koumandou VL, Nisbet RE, Barbrook AC, Howe CJ: Dinoflagellate chloroplasts - where have all the genes gone?. Trends Genet. 2004, 20: 261-267. 10.1016/j.tig.2004.03.008.PubMedView ArticleGoogle Scholar
- von Heijne G: Why mitochondria need a genome. FEBS Lett. 1986, 198: 1-4. 10.1016/0014-5793(86)81172-3.PubMedView ArticleGoogle Scholar
- Popot JL, de Vitry C: On the microassembly of integral membrane proteins. Annu Rev Biophys Biophys Chem. 1990, 19: 369-403. 10.1146/annurev.bb.19.060190.002101.PubMedView ArticleGoogle Scholar
- Claros MG, Perea J, Shu Y, Samatey FA, Popot JL, Jacq C: Limitations to in vivo import of hydrophobic proteins into yeast mitochondria. The case of a cytoplasmically synthesized apocytochrome b. Eur J Biochem. 1995, 228: 762-771.PubMedView ArticleGoogle Scholar
- Wattenberg B, Lithgow T: Targeting of C-terminal (tail)-anchored proteins: understanding how cytoplasmic activities are anchored to intracellular membranes. Traffic. 2001, 2: 66-71. 10.1034/j.1600-0854.2001.20108.x.PubMedView ArticleGoogle Scholar
- Rapaport D: Finding the right organelle. Targeting signals in mitochondrial outer-membrane proteins. EMBO Reports. 2003, 4: 948-952. 10.1038/sj.embor.embor937.PubMedPubMed CentralView ArticleGoogle Scholar
- Horie C, Suzuki H, Sakaguchi M, Mihara K: Targeting and assembly of mitochondrial tail-anchored protein Tom5 to the TOM complex depend on a signal distinct from that of tail-anchored proteins dispersed in the membrane. J Biol Chem. 2003, 278: 41462-41471. 10.1074/jbc.M307047200.PubMedView ArticleGoogle Scholar
- Horie C, Suzuki H, Sakaguchi M, Mihara K: Characterization of signal that directs C-tail-anchored proteins to mammalian mitochondrial outer membrane. Mol Biol Cell. 2002, 13: 1615-1625. 10.1091/mbc.01-12-0570.PubMedPubMed CentralView ArticleGoogle Scholar
- Daley DO, Clifton R, Whelan J: Intracellular gene transfer: reduced hydrophobicity facilitates gene transfer for subunit 2 of cytochrome c oxidase. Proc Natl Acad Sci USA. 2002, 99: 10510-10515. 10.1073/pnas.122354399.PubMedPubMed CentralView ArticleGoogle Scholar
- Perez-Martinez X, Vazquez-Acevedo M, Tolkunova E, Funes S, Claros MG, Davidson E, King MP, Gonzalez-Halphen D: Unusual location of a mitochondrial gene. Subunit III of cytochrome C oxidase is encoded in the nucleus of Chlamydomonad algae. J Biol Chem. 2000, 275: 30144-30152. 10.1074/jbc.M003940200.PubMedView ArticleGoogle Scholar
- Perez-Martinez X, Antaramian A, Vazquez-Acevedo M, Funes S, Tolkunova E, d'Alayer J, Claros MG, Davidson E, King MP, Gonzalez-Halphen D: Subunit II of cytochrome c oxidase in Chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. J Biol Chem. 2001, 276: 11302-11309. 10.1074/jbc.M010244200.PubMedView ArticleGoogle Scholar
- Funes S, Davidson E, Claros MG, van Lis R, Perez-Martinez X, Vazquez-Acevedo M, King MP, Gonzalez-Halphen D: The typically mitochondrial DNA-encoded ATP6 subunit of the F1F0-ATPase is encoded by a nuclear gene in Chlamydomonas reinhardtii. J Biol Chem. 2002, 277: 6051-6058. 10.1074/jbc.M109993200.PubMedView ArticleGoogle Scholar
- Santillan Torres JL, Atteia A, Claros MG, Gonzalez-Halphen D: Cytochrome f and subunit IV, two essential components of the photosynthetic bf complex typically encoded in the chloroplast genome, are nucleus-encoded in Euglena gracilis. Biochim Biophys Acta. 2003, 1604: 180-189.PubMedView ArticleGoogle Scholar
- van Dooren GG, Schwartzbach SD, Osafune T, McFadden GI: Translocation of proteins across the multiple membranes of complex plastids. Biochim Biophys Acta. 2001, 1541: 34-53. 10.1016/S0167-4889(01)00154-9.PubMedView ArticleGoogle Scholar
- Manfredi G, Fu J, Ojaimi J, Sadlock JE, Kwong JQ, Guy J, Schon EA: Rescue of a deficiency in ATP synthesis by transfer of MTATP6, a mitochondrial DNA-encoded gene, to the nucleus. Nat Genet. 2002, 30: 394-399. 10.1038/ng851.PubMedView ArticleGoogle Scholar
- Oca-Cossio J, Kenyon L, Hao H, Moraes CT: Limitations of allotopic expression of mitochondrial genes in mammalian cells. Genetics. 2003, 165: 707-720.PubMedPubMed CentralGoogle Scholar
- Allen JF: Protein phosphorylation in regulation of photosynthesis. Biochim Biophys Acta. 1992, 1098: 275-335.PubMedView ArticleGoogle Scholar
- Allen JF: Control of gene expression by redox potential and the requirement for chloroplast and mitochondrial genomes. J Theor Biol. 1993, 165: 609-631. 10.1006/jtbi.1993.1210.PubMedView ArticleGoogle Scholar
- Race HL, Herrmann RG, Martin W: Why have organelles retained genomes?. Trends Genet. 1999, 15: 364-370. 10.1016/S0168-9525(99)01766-7.PubMedView ArticleGoogle Scholar
- Rodermel S: Pathways of plastid-to-nucleus signaling. Trends Plant Sci. 2001, 6: 471-478. 10.1016/S1360-1385(01)02085-4.PubMedView ArticleGoogle Scholar
- Pfannschmidt T, Schutze K, Fey V, Sherameti I, Oelmuller R: Chloroplast redox control of nuclear gene expression - a new class of plastid signals in interorganellar communication. Antioxid Redox Signal. 2003, 5: 95-101. 10.1089/152308603321223586.PubMedView ArticleGoogle Scholar
- Kanevski I, Maliga P: Relocation of the plastid rbcL gene to the nucleus yields functional ribulose-1,5-bisphosphate carboxylase in tobacco chloroplasts. Proc Natl Acad Sci USA. 1994, 91: 1969-1973.PubMedPubMed CentralView ArticleGoogle Scholar
- John Andrews T, Whitney SM: Manipulating ribulose bisphosphate carboxylase/oxygenase in the chloroplasts of higher plants. Arch Biochem Biophys. 2003, 414: 159-169.PubMedView ArticleGoogle Scholar
- Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ: A mitochondrial specific stress response in mammalian cells. EMBO J. 2002, 21: 4411-4419. 10.1093/emboj/cdf445.PubMedPubMed CentralView ArticleGoogle Scholar
- Adam Z, Clarke AK: Cutting edge of chloroplast proteolysis. Trends Plant Sci. 2002, 7: 451-456. 10.1016/S1360-1385(02)02326-9.PubMedView ArticleGoogle Scholar
- Arnold I, Langer T: Membrane protein degradation by AAA proteases in mitochondria. Biochim Biophys Acta. 2002, 1592: 89-96. 10.1016/S0167-4889(02)00267-7.PubMedView ArticleGoogle Scholar
- Baena-Gonzalez E, Aro EM: Biogenesis, assembly and turnover of photosystem II units. Philos Trans R Soc Lond B Biol Sci. 2002, 357: 1451-1460. 10.1098/rstb.2002.1141.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhang L, Aro EM: Synthesis, membrane insertion and assembly of the chloroplast-encoded D1 protein into photosystem II. FEBS Lett. 2002, 512: 13-18. 10.1016/S0014-5793(02)02218-4.PubMedView ArticleGoogle Scholar
- Ossenbuhl F, Hartmann K, Nickelsen J: A chloroplast RNA binding protein from stromal thylakoid membranes specifically binds to the 5' untranslated region of the psbA mRNA. Eur J Biochem. 2002, 269: 3912-3919. 10.1046/j.1432-1033.2002.03057.x.PubMedView ArticleGoogle Scholar
- Cheung AY, Bogorad L, Van Montagu M, Schnell J: Relocating a gene for herbicide tolerance: A chloroplast gene is converted into a nuclear gene. Proc Nat Acad Sci USA. 1988, 85: 391-395.PubMedPubMed CentralView ArticleGoogle Scholar
- Zerges W: Does complexity constrain organelle evolution?. Trends Plant Sci. 2002, 7: 175-182. 10.1016/S1360-1385(02)02233-1.PubMedView ArticleGoogle Scholar
- Pfanner N, Geissler A: Versatility of the mitochondrial protein import machinery. Nat Rev Mol Cell Biol. 2001, 2: 339-349. 10.1038/35073006.PubMedView ArticleGoogle Scholar
- Palmieri L, Runswick MJ, Fiermonte G, Walker JE, Palmieri F: Yeast mitochondrial carriers: bacterial expression, biochemical identification and metabolic significance. J Bioenerg Biomembr. 2000, 32: 67-77. 10.1023/A:1005564429242.PubMedView ArticleGoogle Scholar
- Dolganov NA, Bhaya D, Grossman AR: Cyanobacterial protein with similarity to the chlorophyll a/b binding proteins of higher plants: evolution and regulation. Proc Natl Acad Sci USA. 1995, 92: 636-640.PubMedPubMed CentralView ArticleGoogle Scholar
- Grossman AR, Bhaya D, Apt KE, Kehoe DM: Light-harvesting complexes in oxygenic photosynthesis: diversity, control, and evolution. Annu Rev Genet. 1995, 29: 231-288. 10.1146/annurev.ge.29.120195.001311.PubMedView ArticleGoogle Scholar
- Strand A, Asami T, Alonso J, Ecker JR, Chory J: Chloroplast to nucleus communication triggered by accumulation of Mg-protoporphyrin IX. Nature. 2003, 421: 79-83. 10.1038/nature01204.PubMedView ArticleGoogle Scholar
- Larkin RM, Alonso JM, Ecker JR, Chory J: GUN4, a regulator of chlorophyll synthesis and intracellular signaling. Science. 2003, 299: 902-906. 10.1126/science.1079978.PubMedView ArticleGoogle Scholar
- Butow RA, Avadhani NG: Mitochondrial signaling; the retrograde response. Mol Cell. 2004, 14: 1-15. 10.1016/S1097-2765(04)00179-0.PubMedView ArticleGoogle Scholar
- Poyton RO, Dagsgaard CJ: Mitochondrial-nuclear crosstalk is involved in oxygen-regulated gene expression in yeast. Adv Exp Med Biol. 2000, 475: 177-184.PubMedView ArticleGoogle Scholar
- Dagsgaard C, Taylor LE, O'Brien KM, Poyton RO: Effects of anoxia and the mitochondrion on expression of aerobic nuclear COX genes in yeast: evidence for a signaling pathway from the mitochondrial genome to the nucleus. J Biol Chem. 2001, 276: 7593-7601. 10.1074/jbc.M009180200.PubMedView ArticleGoogle Scholar
- Contamine V, Picard M: Maintenance and integrity of the mitochondrial genome: a plethora of nuclear genes in the budding yeast. Microbiol Mol Biol Rev. 2000, 64: 281-315. 10.1128/MMBR.64.2.281-315.2000.PubMedPubMed CentralView ArticleGoogle Scholar
- Rasmussen AK, Chatterjee A, Rasmussen LJ, Singh KK: Mitochondria-mediated nuclear mutator phenotype in Saccharomyces cerevisiae. Nucleic Acids Res. 2003, 31: 3909-3917. 10.1093/nar/gkg446.PubMedPubMed CentralView ArticleGoogle Scholar
- Linke B, Nothnagel T, Borner T: Flower development in carrot CMS plants: mitochondria affect the expression of MADS box genes homologous to GLOBOSA and DEFICIENS. Plant J. 2003, 34: 27-37. 10.1046/j.1365-313X.2003.01703.x.PubMedView ArticleGoogle Scholar
- Loeb LA: A mutator phenotype in cancer. Cancer Res. 2001, 61: 3230-3239.PubMedGoogle Scholar
- Allen JF: The function of genomes in bioenergetic organelles. Philos Trans R Soc Lond B Biol Sci. 2003, 358: 19-37. 10.1098/rstb.2002.1191.PubMedPubMed CentralView ArticleGoogle Scholar