New mitochondrial carriers: An overview

Cellular and Molecular Life Sciences

Volumn 62, Issue 19-20, 2005, Pages 2204-2227

  Del Arco, A ^a,b   Satrustegui J ^a  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

^b UNIVERSITY OF CASTILLA LA MANCHA   (Spain)

Author keywords

Gene duplication; Import process; Mitochondrial calcium; Mitochondrial metabolism; Mitochondrial transport; Phylogenetic analysis

Indexed keywords

ACYLCARNITINE; CARNITINE; CITRULLINE; FOLIC ACID; GLUTAMIC ACID; ORNITHINE; S ADENOSYLMETHIONINE;

GENE DUPLICATION; GENE EXPRESSION; GENOME; HUMAN; MITOCHONDRION; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PHYLOGENY; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; UNINDEXED SEQUENCE;

BIOLOGICAL TRANSPORT; CARRIER PROTEINS; GENOME, HUMAN; HUMANS; MITOCHONDRIAL PROTEINS; NUCLEOTIDES; SACCHAROMYCES CEREVISIAE PROTEINS;

MAMMALIA; MINK CELL FOCUS-FORMING VIRUS; SACCHAROMYCES CEREVISIAE;

EID: 27144525581     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-5197-x     Document Type: Review

References (175)

1. LaNoue K. F. and Schoolwerth A. C. (1979) Metabolite transport in mitochondria. Annu. Rev. Biochem. 48: 871-922
2. Palmieri F. (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch. 447: 689-709
3. Kunji E. R. (2004) The role and structure of mitochondrial carriers. FEBS Lett. 564: 239-244
4. Saraste M. and Walker J. E. (1982) Internal sequence repeats and the path of polypeptide in mitochondrial ADP/ATP translocase. FEBS Lett. 144: 250-254
5. Aquila H., Link T. A. and Klingenberg M. (1985) The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane. EMBO J. 4: 2369-2376
6. Indiveri C., Iacobazzi V., Giangregorio N. and Palmieri F. (1997) The mitochondrial carnitine carrier protein: cDNA cloning, primary structure and comparison with other mitochondrial transport proteins. Biochem. J. 321: 713-719
7. Pebay-Peyroula E., Dahout-Gonzalez C., Kahn R., Trezeguet V., Lauquin G. J. and Brandolin G. (2003) Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature 426: 39-44
8. Palmieri L., Rottensteiner H., Girzalsky W., Scarcia P., Palmieri F. and Erdmann R. (2001) Identification and functional reconstitution of the yeast peroxisomal adenine nucleotide transporter. EMBO J. 20: 5049-5059
9. van Roermund C. W., Drissen R., van Den Berg M., Ijlst L., Hettema E. H., Tabak H. F. et al. (2001) Identification of a peroxisomal ATP carrier required for medium-chain fatty acid beta-oxidation and normal peroxisome proliferation in Saccharomyces cerevisiae. Mol. Cell. Biol. 21: 4321-4329
10. Visser W. F., van Roermund C. W., Waterham H. R. and Wanders R. J. (2002) Identification of human PMP34 as a peroxisomal ATP transporter. Biochem. Biophys. Res. Commun. 299: 494-497
11. Dyall S. D., Koehler C. M., Delgadillo-Correa M. G., Bradley P. J., Plumper E., Leuenberger D. et al. (2000) Presence of a member of the mitochondrial carrier family in hydrogenosomes: conservation of membrane-targeting pathways between hydrogenosomes and mitochondria. Mol. Cell. Biol. 20: 2488-2497
12. el Moualij B., Duyckaerts C., Lamotte-Brasseur J. and Sluse F. E. (1997) Phylogenetic classification of the mitochondrial carrier family of Saccharomyces cerevisiae. Yeast 13: 573-581
13. Nelson D. R., Felix C.M. and Swanson J. M. (1998) Highly conserved charge-pair networks in the mitochondrial carrier family. J. Mol. Biol. 277: 285-308
14. Laloi M. (1999) Plant mitochondrial carriers: an overview. Cell. Mol. Life Sci. 56: 918-944
15. Millar A. H. and Heazlewood J. L. (2003) Genomic and proteomic analysis of mitochondrial carrier proteins in Arabidopsis. Plant Physiol. 131: 443-453
16. Picault N., Hodges M., Palmieri L. and Palmieri F. (2004) The growing family of mitochondrial carriers in Arabidopsis. Trends Plant Sci. 9: 138-146
17. Mayor J. A., Kakhniashvili D., Gremse D. A., Campbell C., Kramer R., Schroers A. et al. (1997) Bacterial overexpression of putative yeast mitochondrial transport proteins. J. Bioenerg. Biomembr. 29: 541-547
18. Kakhniashvili D. Mayor J. A., Gremse D. A., Xu Y., Kaplan R. S. (1997) Identification of a novel gene encoding the yeast mitochondrial dicarboxylate transport protein via overexpression, purification and characterization of its protein product. J. Biol. Chem. 272: 4516-4521
19. Palmieri L., Lasorsa F. M., De Palma A., Palmieri F., Runswick M. J. and Walker J. E. (1997) Identification of the yeast ACR1 gene product as a succinate-fumarate transporter essential for growth on ethanol or acetate. FEBS Lett. 417: 114-118
20. Palmieri L., Vozza A., Agrimi G., De Marco V., Runswick M. J., Palmieri F. et al. (1999) Identification of the yeast mitochondrial transporter for oxaloacetate and sulfate. J. Biol. Chem. 274: 22184-22190
21. Fiermonte G., Dolce V., Palmieri L., Ventura M., Runswick M. J., Palmieri F. at al. (2001) Identification of the human mitochondrial oxodicarboxylate carrier. Bacterial expression, reconstitution, functional characterization, tissue distribution, and chromosomal location. J. Biol. Chem. 276: 8225-8230
22. Palmieri, L., Pardo, B., Lasorsa, F. M., del Arco, A., Kobayashi, K., Iijima, M. et al. (2001) Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. EMBO J. 20: 5060-5069
23. Fiermonte G., Palmieri L., Todisco S., Agrimi G., Palmieri F. and Walker JE. (2002) Identification of the mitochondrial glutamate transporter. Bacterial expression, reconstitution, functional characterization and tissue distribution of two human isoforms. J. Biol. Chem. 277: 19289-19294
24. Vozza A., Blanco E., Palmieri L. and Palmieri F. (2004) Identification of the mitochondrial GTP/GDP transporter in Saccharomyces cerevisiae. J. Biol. Chem. 279: 20850-20857
25. Marobbio C. M., Agrimi G., Lasorsa F. M. and Palmieri F. (2003) Identification and functional reconstitution of yeast mitochondrial carrier for S-adenosylmethionine. EMBO J. 22: 5975-5982
26. Agrimi G., Di Noia M. A., Marobbio C. M., Fiermonte G., Lasorsa F. M. and Palmieri F. (2004) Identification of the human mitochondrial S-adenosylmethionine transporter: bacterial expression, reconstitution, functional characterization and tissue distribution. Biochem J. 379: 183-190
27. Marobbio C. M., Vozza A., Harding M., Bisaccia F., Palmieri F. and Walker J. E. (2002) Identification and reconstitution of the yeast mitochondrial transporter for thiamine pyrophosphate. EMBO J. 21: 5653-5661
28. del Arco A. and Satrústegui J. (2004) Identification of a novel human subfamily of mitochondrial carriers with calcium-binding domains. J. Biol. Chem. 279: 24701-24713
29. Fiermonte G., De Leonardis F., Todisco S., Palmieri L., Lasorsa F. M. and Palmieri E (2004) Identification of the mitochondrial ATP-Mg/Pi transporter. Bacterial expression, reconstitution, functional characterization and tissue distribution. J. Biol. Chem. 279: 30722-30730
30. Tzagoloff A., Jang J., Glerum D. M. and Wu M. (1996) FLX1 codes for a carrier protein involved in maintaining a proper balance of flavin nucleotides in yeast mitochondria. J. Biol. Chem. 271: 7392-7397
31. Prohl C., Pelzer W., Diekert K., Kmita H., Bedekovics T. Kispal G. et al. (2001). The yeast mitochondrial carrier Leu5p and its human homologue Graves' disease protein are required for accumulation of coenzyme A in the matrix. Mol. Cell. Biol. 21: 1089-1097
32. Foury F. and Roganti T. (2002) Deletion of the mitochondrial carrier genes MRS3 and MRS4 suppresses mitochondrial iron accumulation in a yeast frataxin-deficient strain. J. Biol. Chem. 277: 4475-4483
33. Kunji E. R. and Harding M. (2003) Projection structure of the atractyloside-inhibited mitochondrial ADP/ATP carrier of Saccharomyces cerevisiae. J. Biol. Chem. 278: 36985-36988
34. Pebay-Peyroula E. and Brandolin G. (2004) Nucleotide exchange in mitochondria: insight at a molecular level. Curr. Opin. Struct. Biol. 14: 420-425
35. Kotaria R., Mayor J. A., Walters D. E. and Kaplan R. S. (1999) Oligomeric state of wild-type and cysteine-less yeast mitochondrial citrate transport proteins. J. Bioenerg. Biomembr. 31: 543-549
36. Schroers A., Burkovski A., Wohlrab H. and Kramer R. (1998) The phosphate carrier from yeast mitochondria. Dimerization is a prerequisite for function. J. Biol. Chem. 273: 14269-14276
37. del Arco A., Agudo M. and Satrustegui J. (2000) Characterization of a second member of the subfamily of calcium-binding mitochondrial carriers expressed in human non-excitable tissues. Biochem. J. 345: 725-732
38. Mashima H., Ueda N., Ohno H., Suzuki J., Ohnishi H., Yasuda H. at al. (2003) A novel mitochondrial Ca2+-dependent solute carrier in the liver identified by mRNA differential display. J. Biol. Chem. 278: 9520-9527
39. del Arco A. and Satrustegui J. (1998) Molecular cloning of Aralar, a new member of the mitochondrial carrier superfamily that binds calcium and is present in human muscle and brain. J. Biol. Chem. 273: 23327-23334
40. Lasorsa F. M., Pinton P., Palmieri L., Fiermonte G., Rizzuto R. and Palmieri F. (2003) Recombinant expression of the Ca(2+)-sensitive aspartate/glutamate carrier increases mitochondrial ATP production in agonist-stimulated Chinese hamster ovary cells. J. Biol. Chem. 278: 38686-38692
41. Roesch K., Hynds P. J., Varga R., Tranebjaerg L. and Koehler C. M. (2004) The calcium-binding aspartate/glutamate carriers, citrin and aralar1, are new substrates for the DDP1/TIMM8a-TIMM13 complex. Hum. Mol. Genet. 13: 2101-2111
42. del Arco, A. (2005) Novel variants of human SCaMC-3, an isoform of the ATP-Mg/Pi mitochondrial carrier, generated by alternative splicing from 3′-flanking transposable elements. Biochem. J. in press 389: 647-655
43. Koehler C. M. (2004) New developments in mitochondrial assembly. Annu. Rev. Cell Dev. Biol. 20: 309-335
44. Rehling P., Brandner K. and Pfanner N. (2004) Mitochondrial import and the twin-pore translocase. Nat. Rev. Mol. Cell Biol. 5: 519-530
45. Mozo T., Fischer K., Flugge U. I. and Schmitz U. K. (1995) The N-terminal extension of the ADP/ATP translocator is not involved in targeting to plant mitochondria in vivo. Plant J. 7: 1015-1020
46. Zara V., Palmieri F., Mahlke K. and Pfanner N. (1992) The cleavable presequence is not essential for import and assembly of the phosphate carrier of mammalian mitochondria but enhances the specificity and efficiency of import. J. Biol. Chem. 267: 12077-12081
47. Koehler C. M., Jarosch E., Tokatlidis K., Schmid K., Schweyen R. J. and Schatz G. (1998) Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science 279: 369-373
48. Curran S. P., Leuenberger D., Schmidt E. and Koehler C. M. (2002) The role of the Tim8p-Tim13p complex in a conserved import pathway for mitochondrial polytopic inner membrane proteins. J. Cell. Biol. 158: 1017-1027
49. Curran S. P., Leuenberger D., Oppliger W. and Koehler C. M. (2002) The Tim9p-Tim10p complex binds to the transmembrane domains of the ADP/ATP carrier. EMBO J. 21: 942-953
50. Koehler C. M., Leuenberger D., Merchant S., Renold A., Junne T. and Schatz G. (1999) Human deafness dystonia syndrome is a mitochondrial disease. Proc. Natl. Acad. Sci. USA 96: 2141-2146
51. Paschen S. A., Rothbauer U., Kaldi K., Bauer M. F., Neupert W. and Brunner M. (2000) The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J. 19: 6392-6400
52. Roesch K., Curran S. P., Tranebjaerg L. and Koehler C. M. (2002) Human deafness dystonia syndrome is caused by a defect in assembly of the DDP1/TIMM8a-TIMM13 complex. Hum. Mol. Genet. 11: 477-486
53. Rothbauer U., Hofmann S., Muhlenbein N., Paschen S. A., Gerbitz K. D., Neupert W. et al. (2001) Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria. J. Biol. Chem. 276: 37327-37334
54. Dolce V., Scarcia P., Iacopetta D. and Palmieri F. (2005) A fourth ADP/ATP carrier isoform in man: identification, bacterial expression, functional characterization and tissue distribution. FEBS Lett. 579: 633-637
55. Sekoguchi E., Sato N., Yasui A., Fukada S., Nimura Y., Aburatani H. et al. (2003) A novel mitochondrial carnitine-acylcarnitine translocase induced by partial hepatectomy and fasting. J. Biol. Chem. 278: 38796-38802
56. Xu X., Shi Y. C., Gao W., Mao G., Zhao G., Agrawal S. et al. (2002) The novel presenilin-1-associated protein is a proapoptotic mitochondrial protein. J. Biol. Chem. 277: 48913-48922
57. Yerushalmi G. M., Leibowitz-Amit R., Shaharabany M. and Tsarfaty I. (2002) Met-HGF/SF signal transduction induces mimp, a novel mitochondrial carrier homologue, which leads to mitochondrial depolarization. Neoplasia 4: 510-522
58. Wang B., Li N., Sui L., Wu Y., Wang X., Wang Q. et al. (2004) HuBMSC-MCP, a novel member of mitochondrial carrier superfamily, enhances dendritic cell endocytosis. Biochem. Biophys. Res. Commun. 314: 292-300.
59. Sesaki H. and Jensen R. E. (2001) UGO1 encodes an outer membrane protein required for mitochondrial fusion. J. Cell. Biol. 152: 1123-1134
60. Long M., Betran E., Thornton K. and Wang W. (2003) The origin of new genes: glimpses from the young and old. Nat. Rev. Genet. 4: 865-875
61. Hurles M. (2004) Gene duplication: the genomic trade in spare parts. PLoS Biol. 2: E206.
62. Dietrich F. S., Voegeli S., Brachat S., Lerch A., Gates K., Steiner S. et al. (2004) The Ashbya gossypii genome as a tool for mapping the ancient Saccharomyces cerevisiae genome. Science 304: 304-307.
63. Kellis M., Birren B. W. and Lander E. S. (2004) Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428: 617-624
64. Tan M. G., Ooi L. L., Aw S. E. and Hui K. M. (2004) Cloning and identification of hepatocellular carcinoma down-regulated mitochondrial carrier protein, a novel liver-specific uncoupling protein. J. Biol. Chem. 279: 45235-45244
65. Kao L. R., Megraw T. L. and Chae C. B. (1996) SHM1: a multicopy suppressor of a temperature-sensitive null mutation in the HMG1-like abf2 gene. Yeast 12: 1239-1250
66. Cho J. H., Ha S. J., Kao L. R., Megraw T. L. and Chae C. B. (1998) A novel DNA-binding protein bound to the mitochondrial inner membrane restores the null mutation of mitochondrial histone Abf2p in Saccharomyces cerevisiae. Mol. Cell. Biol. 18: 5712-5723
67. Lesuisse E., Lyver E. R., Knight S. A. and Dancis A. (2004) Role of YHM1, encoding a mitochondrial carrier protein, in iron distribution of yeast. Biochem. J. 378: 599-607
68. Fiermonte G., Dolce V. and Palmieri F. (1998) Expression in Escherichia coli, functional characterization and tissue distribution of isoforms A and B of the phosphate carrier from bovine mitochondria. J. Biol. Chem. 273: 22782-22787
69. Phelps A., Schobert C. T. and Wohlrab H. (1991) Cloning and characterization of the mitochondrial phosphate transport protein gene from the yeast Saccharomyces cerevisiae. Biochemistry 30: 248-252
70. Takabatake R., Siddique A. B., Kouchi H., Izui K. and Hata S. (2001) Characterization of a Saccharomyces cerevisiae gene that encodes a mitochondrial phosphate transporter-like protein. J. Biochem. 129: 827-833
71. Wohlrab H., Annese V. and Haefele A. (2002) Single replacement constructs of all hydroxyl, basic and acidic amino acids identify new function and structure-sensitive regions of the mitochondrial phosphate transport protein. Biochemistry 41: 3254-3261
72. Hamel P., Saint-Georges Y., de Pinto B., Lachacinski N., Altamura N. and Dujardin G. (2004) Redundancy in the function of mitochondrial phosphate transport in Saccharomyces cerevisiae and Arabidopsis thaliana. Mol. Microbiol. 51: 307-317
73. Dujon B., Sherman D., Fischer G., Durrens P., Casaregola S., Lafontaine I. et al. (2004) Genome evolution in yeasts. Nature 430: 35-44
74. Camacho J. A., Rioseco-Camacho N., Andrade D., Porter J. and Kong J. (2003) Cloning and characterization of human ORNT2: a second mitochondrial ornithine transporter that can rescue a defective ORNT1 in patients with the hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, a urea cycle disorder. Mol. Genet. Metab. 79: 257-271
75. Fiermonte G., Dolce V., David L., Santorelli F. M., Dionisi-Vici C., Palmieri F. et al. (2003) The mitochondrial ornithine transporter. Bacterial expression, reconstitution, functional characterization and tissue distribution of two human isoforms. J. Biol. Chem. 278: 32778-32783
76. Pande S. V. (1975) A mitochondrial carnitine acylcarnitine translocase system. Proc. Natl. Acad. Sci. USA 72: 883-887
77. Huizing M., Iacobazzi V., Ijlst L., Savelkoul P., Ruitenbeek W., van den Heuvel L. et al. (1997) Cloning of the human carnitine-acylcarnitine carrier cDNA and identification of the molecular defect in a patient. Am. J. Hum. Genet. 61: 1239-1245
78. van Roermund C. W., Hettema E. H., van den Berg M., Tabak H. F. and Wanders R. J. (1999) Molecular characterization of carnitine-dependent transport of acetyl-CoA from peroxisomes to mitochondria in Saccharomyces cerevisiae and identification of a plasma membrane carnitine transporter, Agp2p. EMBO J. 18: 5843-5852
79. Zhang P., Gu Z. and Li W. H. (2003) Different evolutionary patterns between young duplicate genes in the human genome. Genome Biol. 4: R56
80. Indiveri C., Tonazzi A., Stipani I. and Palmieri F. (1997) The purified and reconstituted ornithine/citrulline carrier from rat liver mitochondria: electrical nature and coupling of the exchange reaction with H+ translocation. Biochem. J. 327: 349-355
81. Camacho J. A., Obie C., Biery B., Goodman B. K., Hu C. A , Almashanu S. et al. (1999) Hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome is caused by mutations in a gene encoding a mitochondrial ornithine transporter. Nat. Genet. 22: 151-158
82. Kramer R., Kurzinger G. and Heberger C. (1986) Isolation and functional reconstitution of the aspartate/glutamate carrier from mitochondria. Arch. Biochem. Biophys. 251: 166-174
83. Dierks T., Riemer E. and Kramer R. (1988) Reaction mechanism of the reconstituted aspartate/glutamate carrier from bovine heart mitochondria. Biochim. Biophys. Acta 943: 231-244
84. Kobayashi K., Sinasac D. S., Iijima M., Boright A. P., Begum L., Lee J. R. et al. (1999) The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein. Nat. Genet. 22: 159-163
85. del Arco A., Morcillo J., Martinez-Morales J. R., Galian C., Martos V. et al. (2002) Expression of the aspartate/glutamate mitochondrial carriers aralar1 and citrin during development and in adult rat tissues. Eur. J. Biochem. 269: 3313-3320
86. Ramos M., del Arco A., Pardo B., Martinez-Serrano A., Martinez-Morales J. R., Kobayashi K. et al (2003) Developmental changes in the Ca2+-regulated mitochondrial aspartate-glutamate carrier aralar1 in brain and prominent expression in the spinal cord. Brain Res. Dev. Brain Res. 143: 33-46
87. Cavero S., Vozza A., del Arco A., Palmieri L., Villa A., Blanco E. et al. (2003) Identification and metabolic role of the mitochondrial aspartate-glutamate transporter in Saccharomyces cerevisiae. Mol. Microbiol. 50: 1257-1269
88. Sinasac D. S., Moriyama M., Jalil M. A., Begum L., Li M. X., Iijima M. et al. (2004) Slc25a13-knockout mice harbor metabolic deficits but fail to display hallmarks of adult-onset type II citrullinemia. Mol. Cell. Biol. 24: 527-536
89. Rubi B., del Arco A., Bartley C., Satrústegui J. and Maechler P. (2004) The malate-aspartate NADH shuttle member Aralar1 determines glucose metabolic fate, mitochondrial activity, and insulin secretion in beta cells. J. Biol. Chem. 279: 55659-55666
90. Leverve X. M., Verhoeven A. J., Groen A. K., Meijer A. J. and Tager J. M. (1986) The malate/aspartate shuttle and pyruvate kinase as targets involved in the stimulation of gluconeogenesis by phenylephrine. Eur. J. Biochem. 155: 551-556
91. Sugano T., Nishimura K., Sogabe N., Shiota M., Oyama N., Noda S. et al. (1988) Ca2+-dependent activation of the malate-aspartate shuttle by norepinephrine and vasopressin in perfused rat liver. Arch. Biochem. Biophys. 264: 144-154
92. Scaduto R. C. Jr (1994) Calcium and 2-oxoglutarate-mediated control of aspartate formation by rat heart mitochondria. Eur. J. Biochem. 223: 751-758
93. O'Donnell J. M., Kudej R. K., LaNoue K. F., Vatner S. F. and Lewandowski E. D. (2004) Limited transfer of cytosolic NADH into mitochondria at high cardiac workload. Am. J. Physiol. Heart Circ. Physiol. 286: H2237-2242
94. Ramoz N., Reichert J. G., Smith C. J., Silverman J. M., Bespalova I. N., Davis K. L. et al. (2004) Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. Am. J. Psychiatry 161: 662-669
95. Molinari F., Raas-Rothschild A., Rio M., Fiermonte G., Encha-Razavi F., Palmieri L. et al. (2005) Impaired mitochondrial glutamate transport in autosomal recessive neonatal myoclonic epilepsy. Am. J. Hum. Genet. 76: 334-339
96. Dolce V., Fiermonte G., Runswick M. J., Palmieri F. and Walker J. E. (2001) The human mitochondrial deoxynucleotide carrier and its role in the toxicity of nucleoside antivirals. Proc. Natl. Acad. Sci. USA 98: 2284-2288
97. Tjaden J., Haferkamp I., Boxma B., Tielens A. G., Huynen M. and Hackstein J. H. (2004) A divergent ADP/ATP carrier in the hydrogenosomes of Trichomonas gallinae argues for an independent origin of these organelles. Mol. Microbiol. 51: 1439-1446
98. Austin J. and Aprille J. R. (1984) Carboxyatractyloside-insensitive influx and efflux of adenine nucleotides in rat liver mitochondria. J. Biol. Chem. 259: 154-160
99. Sutton R. and Pollak J. K. (1980) Hormone-initiated maturation of rat liver mitochondria after birth. Biochem. J. 186: 361-367
100. Aprille J. R. (1988) Regulation of the mitochondrial adenine nucleotide pool size in liver: mechanism and metabolic role. FASEB J. 2: 2547-2556
101. Joyal J. L. and Aprille J. R. (1992) The ATP-Mg/Pi carrier of rat liver mitochondria catalyzes a divalent electroneutral exchange. J. Biol. Chem. 267: 19198-19203
102. Klingenberg M. (1979) Overview of mitochondrial metabolite transport systems. Methods Enzymol. 56: 245-252
103. Nosek M. T., Dransfield D. T. and Aprille J. R. (1990) Calcium stimulates ATP-Mg/Pi carrier activity in rat liver mitochondria. J. Biol. Chem. 265: 8444-8450
104. Chen X. J. (2004) Sal1p, a calcium-dependent carrier protein that suppresses an essential cellular function associated With the Aac2 isoform of ADP/ATP translocase in Saccharomyces cerevisiae. Genetics 167: 607-617
105. Drgon, T., Sabova L., Nelson N. and Kolarov J. (1991) ADP/ATP translocator is essential only for anaerobic growth of yeast Saccharomyces cerevisiae. FEBS Lett. 289: 159-162
106. Aprille J. R. and Austin J. (1981) Regulation of the mitochondrial adenine nucleotide pool size. Arch. Biochem. Biophys. 212: 689-699
107. van der Giezen M., Slotboom D. J., Horner D. S., Dyal P. L., Harding M., Xue G. P. et al. (2002) Conserved properties of hydrogenosomal and mitochondrial ADP/ATP carriers: a common origin for both organelles. EMBO J. 21: 572-579
108. Voncken F., Boxma B., Tjaden J., Akhmanova A., Huynen M., Verbeek F. et al. (2002) Multiple origins of hydrogenosomes: functional and phylogenetic evidence from the ADP/ATP carrier of the anaerobic chytrid Neocallimastix sp. Mol. Microbiol. 44: 1441-1454
109. Hackstein J. H., Akhmanova A., Boxma B., Harhangi H. R. and Voncken F. G. (1999) Hydrogenosomes: eukaryotic adaptations to anaerobic environments. Trends Microbiol. 7: 441-447
110. Hrdy I., Hirt R. P., Dolezal P., Bardonova L., Foster P. G., Tachezy J. et al. (2004) Trichomonas hydrogenosomes contain the NADH dehydrogenase module of mitochondrial complex I. Nature 432: 618-622
111. Boxma B., de Graaf R. M., van der Staay G. W., van Alen T. A., Ricard G., Gabaldon T. et al. (2005) An anaerobic mitochondrion that produces hydrogen. Nature 434: 74-79
112. Keeling P. J. and Palmer J. D. (2000) Parabasalian flagellates are ancient eucaryotes. Nature 405: 635-637
113. Rosenberg M. J., Agarwala R., Bouffard G., Davis J., Fiermonte G., Hilliard M. S. et al. (2002) Mutant deoxynucleotide carrier is associated with congenital microcephaly. Nat. Genet. 32: 175-179
114. Kelley R. I., Robinson D., Puffenberger E. G., Strauss K. A. and Morton D. H. (2002) Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria. Am. J. Med. Genet. 112: 318-326
115. Lam W., Chen C., Ruan S., Leung C. H. and Cheng Y. C. (2005) Expression of deoxynucleotide carrier is not associated with the mitochondrial DNA depletion caused by anti-HIV dideoxynucleoside analogs and mitochondrial dNTP uptake. Mol. Pharmacol. 67: 408-416
116. Bridges E. G., Jiang Z. and Cheng Y. C. (1999) Characterization of a dCTP transport activity reconstituted from human mitochondria. J. Biol. Chem. 274: 4620-4625
117. Lai Y., Tse C. M. and Unadkat J. D. (2004) Mitochondrial expression of the human equilibrative nucleoside transporter 1 (hENT1) results in enhanced mitochondrial toxicity of antiviral drugs. J. Biol. Chem. 279: 4490-4497
118. Bradshaw P. C. and Samuels D. C. (2005) A computational model of mitochondrial deoxynucleotide metabolism and DNA replication. Am. J. Physiol. Cell Physiol. 288: C989-1002
119. Esposito L. A., Melov S., Panov A., Cottrell B.A. and Wallace D. C. (1999) Mitochondrial disease in mouse results in increased oxidative stress. Proc. Natl. Acad. Sci. USA. 96: 4820-4825
120. Elpeleg O., Mandel H. and Saada A. (2002) Depletion of the other genome-mitochondrial DNA depletion syndromes in humans. J. Mol. Med. 80: 389-396
121. Van Veldhoven P. P., Just W. W. and Mannaerts G. P. (1987) Permeability of the peroxisomal membrane to cofactors of beta-oxidation. Evidence for the presence of a pore-forming protein. J. Biol. Chem. 262: 4310-4318
122. Dansen T. B., Wirtz K. W., Wanders R. J. and Pap E. H. (2000) Peroxisomes in human fibroblasts have a basic pH. Nat. Cell. Biol. 2: 51-53
123. Antonenkov V. D., Sormunen R. T. and Hiltunen J. K. (2004) The rat liver peroxisomal membrane forms a permeability barrier for cofactors but not for small metabolites in vitro. J. Cell. Sci. 117: 5633-5642
124. Hettema E. H. and Tabak H. F. (2000) Transport of fatty acids and metabolites across the peroxisomal membrane. Biochim. Biophys. Acta 1486: 18-27
125. Jank B., Habermann B., Schweyen R. J. and Link T. A. (1993) PMP47, a peroxisomal homologue of mitochondrial solute carrier proteins. Trends Biochem. Sci. 18: 427-428
126. Nakagawa T., Imanaka T., Morita M., Ishiguro K., Yurimoto H., Yamashita A. et al. (2000) Peroxisomal membrane protein Pmp47 is essential in the metabolism of middle-chain fatty acid in yeast peroxisomes and Is associated with peroxisome proliferation. J. Biol. Chem. 275: 3455-3461
127. van Roermund C. W., Waterham H. R., Ijlst L. and Wanders R. J. (2003) Fatty acid metabolism in Saccharomyces cerevisiae. Cell. Mol. Life Sci. 60: 1838-1851
128. Lasorsa F. M., Scarcia P., Erdmann R., Palmieri F., Rottensteiner H. and Palmieri L. (2004) The yeast peroxisomal adenine nucleotide transporter: characterization of two transport modes and involvement in DeltapH formation across peroxisomal membranes. Biochem. J. 381: 581-585
129. McKee E. E., Bentley A. T., Smith R. M. Jr and Ciaccio C. E. (1999) Origin of guanine nucleotides in isolated heart mitochondria. Biochem. Biophys. Res. Commun. 257: 466-472
130. McKee E. E., Bentley A. T., Smith R. M. Jr, Kraas J. R. and Ciaccio C. E. (2000) Guanine nucleotide transport by atractyloside-sensitive and -insensitive carriers in isolated heart mitochondria. Am. J. Physiol. Cell. Physiol. 279: C1870-1879
131. Horne D. W., Holloway R. S. and Wagner C. (1997) Transport of S-adenosylmethionine in isolated rat liver mitochondria. Arch. Biochem. Biophys. 343: 201-206
132. Lalo D., Stettler S., Mariotte S., Gendreau E. and Thuriaux P. (1994) Organization of the centromeric region of chromosome XIV in Saccharomyces cerevisiae. Yeast 10: 523-533
133. Titus S.A. and Moran R. G. (2000) Retrovirally mediated complementation of the glyB phenotype. Cloning of a human gene encoding the carrier for entry of folates into mitochondria. J. Biol. Chem. 275: 36811-36817
134. McCarthy E. A., Titus S. A., Taylor S. M., Jackson-Cook C. and Moran R. G. (2004) A mutation inactivating the mitochondrial inner membrane folate transporter creates a glycine requirement for survival of chinese hamster cells. J. Biol. Chem. 279: 33829-33836
135. Horne D. W., Holloway R. S. and Said H. M. (1992) Uptake of 5-formyltetrahydrofolate in isolated rat liver mitochondria is carrier-mediated. J. Nutr. 122: 2204-2209
136. McBurney M. W. and Whitmore G. F. (1974) Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells. Cell 2: 173-182
137. Hildyard J. C. and Halestrap A. P. (2003) Identification of the mitochondrial pyruvate carrier in Saccharomyces cerevisiae. Biochem J. 374: 607-611
138. Bafunno V., Giancaspero T. A., Brizio C., Bufano D., Passarella S., Boles E. et al. (2004) Riboflavin uptake and FAD synthesis in Saccharomyces cerevisiae mitochondria: involvement of the Flx1p carrier in FAD export. J. Biol. Chem. 279: 95-102
139. Kolisek M., Zsurka G., Samaj J., Weghuber J., Schweyen R. J. and Schweigel M. (2003) Mrs2p is an essential component of the major electrophoretic Mg2+ influx system in mitochondria. EMBO J. 22: 1235-1244
140. Wiesenberger G., Link T. A., von Ahsen U., Waldherr M. and Schweyen R. J. (1991) MRS3 and MRS4, two suppressors of mtRNA splicing defects in yeast, are new members of the mitochondrial carrier family. J. Mol. Biol. 217: 23-37
141. Van Dyck E., Jank B., Ragnini A., Schweyen R. J., Duyckaerts C., Sluse F. et al. (1995) Overexpression of a novel member of the mitochondrial carrier family rescues defects in both DNA and RNA metabolism in yeast mitochondria. Mol. Gen. Genet. 246: 426-436
142. Muhlenhoff U., Stadler J. A., Richhardt N., Seubert A., Eickhorst T., Schweyen R. J. et al. (2003) A specific role of the yeast mitochondrial carriers MRS3/4p in mitochondrial iron acquisition under iron-limiting conditions. J. Biol. Chem. 278: 40612-40620
143. Rutherford J. C., Jaron S., Ray E., Brown P. O. and Winge D. R. (2001) A second iron-regulatory system in yeast independent of Aft1p. Proc. Natl. Acad. Sci. USA 98: 14322-14327
144. Li L. and Kaplan J. (2004) A mitochondrial-vacuolar signaling pathway in yeast that affects iron and copper metabolism. J. Biol. Chem. 279: 33653-33661
145. Foury F. (1999) Low iron concentration and aconitase deficiency in a yeast frataxin homologue deficient strain. FEBS Lett. 456: 281-284
146. Lange H., Kispal G. and Lill R. (1999) Mechanism of iron transport to the site of heme synthesis inside yeast mitochondria. J. Biol. Chem. 274: 18989-18996
147. Li F. Y., Nikali K., Gregan J., Leibiger I., Leibiger B., Schweyen R. et al. (2001) Characterization of a novel human putative mitochondrial transporter homologous to the yeast mitochondrial RNA splicing proteins 3 and 4. FEBS Lett. 494: 79-84
148. Li Q. Z., Eckenrode S., Ruan Q. G., Wang C. Y., Shi J. D., McIndoe R. A. et al. (2001) Rapid decrease of RNA level of a novel mouse mitochondria solute carrier protein (Mscp) gene at 4-5 weeks of age. Mamm. Genome 12: 830-836
149. Luk E., Carroll M., Baker M. and Culotta V. C. (2003) Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1, a member of the mitochondrial carrier family. Proc. Natl. Acad. Sci. USA. 100: 10353-10357
150. Yu X. X., Lewin D. A., Zhong A., Brush J., Schow P. W., Sherwood S. W. et al. (2001) Overexpression of the human 2-oxoglutarate carrier lowers mitochondrial membrane potential in HEK-293 cells: contrast with the unique cold-induced mitochondrial carrier CGI-69. Biochem. J. 353: 369-375
151. Crompton M., Palmieri F., Capano M. and Quagliariello E. (1975) A kinetic study of sulphate transport in rat liver mitochondria. Biochem. J. 146: 667-673
152. Saris N. E. (1980) Sulphate transport by H+ symport and by the dicarboxylate carrier in mitochondria. Biochem. J. 192: 911-917
153. Balk J. and Lill R. (2004) The cell's cookbook for iron-sulfur clusters: recipes for fool's gold? Chembiochem 5: 1044-1049
154. Sugden M. C. and Holness M. J. (2003) Trials, tribulations and finally, a transporter: the identification of the mitochondrial pyruvate transporter. Biochem. J. 374: 1-2
155. Douce, R. (1985) Mitochondria in Higher Plants. Structure, Function and Biogenesis, pp. 1-327, Academic Press, New York
156. Neuburger, M. and Douce, R. (1983) Slow passive diffusion of NAD+ between intact isolated plant mitochondria and suspending medium. Biochem. J. 216: 443-450
157. Rustin P., Parfait B., Chretien D., Bourgeron T., Djouadi F., Bastin J. et al. (1996) Fluxes of nicotinamide adenine dinucleotides through mitochondrial membranes in human cultured cells. J. Biol. Chem. 271: 14785-14790
158. Haferkamp I., Schmitz-Esser S., Linka N., Urbany C., Collingro A., Wagner M. et al. (2004) A candidate NAD+ transporter in an intracellular bacterial symbiont related to Chlamydiae. Nature 432: 622-625
159. Schmitz-Esser S., Linka N., Collingro A., Beier C. L., Neuhaus H. E., Wagner M. et al. (2004) ATP/ADP translocases: a common feature of obligate intracellular amoebal symbionts related to Chlamydiae and Rickettsiae. J. Bacteriol. 186: 683-691
160. Porter R. K., Scott J. M. and Brand M. D. (1992) Choline transport into rat liver mitochondria. Characterization and kinetics of a specific transporter. J. Biol. Chem. 267: 14637-14646
161. Rossi L., Serafini S., Schiavano G. F., Casablanca A., Vallanti G., Chiarantini L. et al. (1999) Metabolism, mitochondrial uptake and toxicity of 2′, 3′-dideoxycytidine. Biochem. J. 344: 915-920
162. Kvamme E., Roberg B. and Torgner I. A. (2000) Glutamine transport in brain mitochondria. Neurochem. Int. 37: 131-138
163. Indiveri C., Abruzzo G., Stipani I. and Palmieri F. (1998) Identification and purification of the reconstitutively active glutamine carrier from rat kidney mitochondria. Biochem. J. 333: 285-290
164. Soboll S., Lenzen C., Rettich D., Grundel S. and Ziegler B. (1991) Characterisation of glutamine uptake in rat liver mitochondria. Eur. J. Biochem. 197: 113-117
165. Miyake S., Yamashita T., Taniguchi M., Tamatani M., Sato K. and Tohyama M. (2002) Identification and characterization of a novel mitochondrial tricarboxylate carrier. Biochem. Biophys. Res. Commun. 295: 463-468
166. Chen Z., Putt D. and Lash L. H. (2000) Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria: further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport. Arch. Biochem. Biophys. 373: 193-202
167. Coll O., Colell A., Garcia-Ruiz C., Kaplowitz N. and Fernandez-Checa J. C. (2003) Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology 38: 692-702
168. Martensson J., Lai J. C. and Meister A. (1990) High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function. Proc. Natl. Acad. Sci. USA 87: 7185-7189
169. Powell S. J., Medd S. M., Runswick M. J. and Walker J. E. (1989) Two bovine genes for mitochondrial ADP/ATP translocase expressed differences in various tissues. Biochemistry 28: 866-873
170. Kaplan R. S., Mayor J. A. and Wood D. O. (1993) The mitochondrial tricarboxylate transport protein. cDNA cloning, primary structure and comparison with other mitochondrial transport proteins. J. Biol. Chem. 268: 13682-13690
171. Mayor J. A., Kakhniashvili D., Gremse D. A., Campbell C., Kramer R., Schroers A. et al. (1997) Bacterial overexpression of putative yeast mitochondrial transport proteins. J. Bioenerg. Biomembr. 29: 541-547
172. Fleury C., Neverova M., Collins S., Raimbault S., Champigny O., Levi-Meyrueis C. et al. (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat. Genet. 15: 269-272
173. Mao W., Yu X. X., Zhong A., Li W., Brush J., Sherwood S. W. et al. (1999) UCP4, a novel brain-specific mitochondrial protein that reduces membrane potential in mammalian cells. FEBS Lett. 443: 326-330
174. Haguenauer A., Raimbault S., Masscheleyn S., Gonzalez-Barroso M. D., Criscuolo F., Plamondon J. et al. (2005) A new renal mitochondrial carrier, KMCP1, is upregulated during tubular cell regeneration and induction of antioxidant enzymes. J. Biol. Chem. 280: 22036-22043
175. Sanchis D., Fleury C., Chomiki N., Goubern M., Huang Q., Neverova M. et al. (1998) BMCP1, a novel mitochondrial carrier with high expression in the central nervous system of humans and rodents, and respiration uncoupling activity in recombinant yeast. J. Biol. Chem. 273: 34611-34615