Skip to main content

Advertisement

Log in

The mitochondrial complex I of trypanosomatids - an overview of current knowledge

  • Mini-Review
  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

The contribution of trypanosomatid mitochondrial complex I for energy transduction has long been debated. Herein, we summarize current knowledge on the composition and relevance of this enzyme. Bioinformatic and proteomic analyses allowed the identification of many conserved and trypanosomatid-specific subunits of NADH:ubiquinone oxidoreductase, revealing a multifunctional enzyme capable of performing bioenergetic activities and possibly, also of functioning in fatty acid metabolism. A multimeric structure organized in 5 domains of more than 2 MDa is predicted, in contrast to the 1 MDa described for mammalian complex I. The relevance of mitochondrial complex I within the Trypanosomatidae family is quite diverse with its NADH oxidation activity being dispensable for both procyclic and bloodstream Trypanosoma brucei, whereas in Phytomonas serpens the enzyme is the only respiratory complex able to sustain membrane potential. Aside from complex I, trypanosomatid mitochondria contain a type II NADH dehydrogenase and a NADH-dependent fumarate reductase as alternative electron entry points into the respiratory chain and thus, some trypanosomatids may have bypassed the need for complex I. The involvement of each of these enzymes in the maintenance of the mitochondrial redox balance in trypanosomatids is still an open question and requires further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Abdrakhmanova A, Zwicker K, Kerscher S, Zickermann V, Brandt U (2006) Tight binding of NADPH to the 39-kDa subunit of complex I is not required for catalytic activity but stabilizes the multiprotein complex. Biochim Biophys Acta 1757(12):1676–1682

    CAS  Google Scholar 

  • Acestor N, Zikova A, Dalley RA, Anupama A, Panigrahi AK et al (2011) Trypanosoma brucei mitochondrial respiratome: composition and organization in procyclic form. Mol Cell Proteomics 10(9):M110 006908

    Google Scholar 

  • Angerer H (2013) The superfamily of mitochondrial Complex1_LYR motif-containing (LYRM) proteins. Biochem Soc Trans 41(5):1335–1341

    CAS  Google Scholar 

  • Angerer H, Radermacher M, Malkowska M, Steger M, Zwicker K et al (2014) The LYR protein subunit NB4M/NDUFA6 of mitochondrial complex I anchors an acyl carrier protein and is essential for catalytic activity. Proc Natl Acad Sci U S A 111(14):5207–5212

    CAS  Google Scholar 

  • Bald D, Koul A (2010) Respiratory ATP synthesis: the new generation of mycobacterial drug targets? FEMS Microbiol Lett 308:1–7

    CAS  Google Scholar 

  • Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E et al (2012) NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab 16(3):378–386

    CAS  Google Scholar 

  • Baradaran R, Berrisford JM, Minhas GS, Sazanov LA (2013) Crystal structure of the entire respiratory complex I. Nature 494(7438):443–448

    CAS  Google Scholar 

  • Beattie DS, Howton MM (1996) The presence of rotenone-sensitive NADH dehydrogenase in the long slender bloodstream and the procyclic forms of Trypanosoma brucei brucei. Eur J Biochem 241(3):888–894

    CAS  Google Scholar 

  • Beattie DS, Obungu VH, Kiaira JK (1994) Oxidation of NADH by a rotenone and antimycin-sensitive pathway in the mitochondrion of procyclic Trypanosoma brucei brucei. Mol Biochem Parasitol 64(1):87–94

    CAS  Google Scholar 

  • Benne R (1989) RNA-editing in trypanosome mitochondria. Biochim Biophys Acta 1007(2):131–139

    CAS  Google Scholar 

  • Bermudez R, Dagger F, D’Aquino JA, Benaim G, Dawidowicz K (1997) Characterization of mitochondrial electron-transfer in Leishmania mexicana. Mol Biochem Parasitol 90(1):43–54

    CAS  Google Scholar 

  • Besteiro S, Barrett MP, Riviere L, Bringaud F (2005) Energy generation in insect stages of Trypanosoma brucei: metabolism in flux. Trends Parasitol 21(4):185–191

    CAS  Google Scholar 

  • Biagini GA, Fisher N, Shone AE, Mubaraki MA, Srivastava A et al (2012) Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria. Proc Natl Acad Sci U S A 109(21):8298–8303

    CAS  Google Scholar 

  • Biagini GA, Viriyavejakul P, O’Neill PM, Bray PG, Ward SA (2006) Functional characterization and target validation of alternative complex I of Plasmodium falciparum mitochondria. Antimicrob Agents Chemother 50(5):1841–1851

    CAS  Google Scholar 

  • Brandt U (2006) Energy converting NADH:quinone oxidoreductase (complex I). Annu Rev Biochem 75:69–92

    CAS  Google Scholar 

  • Brockmann C, Diehl A, Rehbein K, Strauss H, Schmieder P et al (2004) The oxidized subunit B8 from human complex I adopts a thioredoxin fold. Structure 12(9):1645–1654

    CAS  Google Scholar 

  • Buschges R, Bahrenberg G, Zimmermann M, Wolf K (1994) NADH: ubiquinone oxidoreductase in obligate aerobic yeasts. Yeast 10(4):475–479

    CAS  Google Scholar 

  • Bych K, Kerscher S, Netz DJ, Pierik AJ, Zwicker K et al (2008) The iron-sulphur protein Ind1 is required for effective complex I assembly. EMBO J 27(12):1736–1746

    CAS  Google Scholar 

  • Cardol P (2011) Mitochondrial NADH:ubiquinone oxidoreductase (complex I) in eukaryotes: a highly conserved subunit composition highlighted by mining of protein databases. Biochim Biophys Acta 1807(11):1390–1397

    CAS  Google Scholar 

  • Cardol P, Vanrobaeys F, Devreese B, Van Beeumen J, Matagne RF et al (2004) Higher plant-like subunit composition of mitochondrial complex I from Chlamydomonas reinhardtii: 31 conserved components among eukaryotes. Biochim Biophys Acta 1658(3):212–224

    CAS  Google Scholar 

  • Carneiro P, Duarte M, Videira A (2004) The main external alternative NAD(P)H dehydrogenase of Neurospora crassa mitochondria. Biochim Biophys Acta 1608(1):45–52

    CAS  Google Scholar 

  • Carranza JC, Kowaltowski AJ, Mendonca MA, de Oliveira TC, Gadelha FR et al (2009) Mitochondrial bioenergetics and redox state are unaltered in Trypanosoma cruzi isolates with compromised mitochondrial complex I subunit genes. J Bioenerg Biomembr 41(3):299–308

    Google Scholar 

  • Carroll J, Fearnley IM, Skehel JM, Runswick MJ, Shannon RJ et al (2005) The post-translational modifications of the nuclear encoded subunits of complex I from bovine heart mitochondria. Mol Cell Proteomics 4(5):693–699

    CAS  Google Scholar 

  • Carroll J, Fearnley IM, Skehel JM, Shannon RJ, Hirst J et al (2006) Bovine complex I is a complex of 45 different subunits. J Biol Chem 281(43):32724–32727

    CAS  Google Scholar 

  • Cermakova P, Verner Z, Man P, Lukes J, Horvath A (2007) Characterization of the NADH:ubiquinone oxidoreductase (complex I) in the trypanosomatid Phytomonas serpens (Kinetoplastida). FEBS J 274(12):3150–3158

    CAS  Google Scholar 

  • Chen M, Bennedsen M, Zhai L, Kharazmi A (2001) Purification and enzymatic activity of an NADH-fumarate reductase and other mitochondrial activities of Leishmania parasites. APMIS 109(12):801–808

    CAS  Google Scholar 

  • Chen R, Fearnley IM, Peak-Chew SY, Walker JE (2004) The phosphorylation of subunits of complex I from bovine heart mitochondria. J Biol Chem 279(25):26036–26045

    CAS  Google Scholar 

  • Clayton AM, Guler JL, Povelones ML, Gluenz E, Gull K et al (2011) Depletion of mitochondrial acyl carrier protein in bloodstream-form Trypanosoma brucei causes a kinetoplast segregation defect. Eukaryot Cell 10(3):286–292

    CAS  Google Scholar 

  • Coustou V, Besteiro S, Riviere L, Biran M, Biteau N et al (2005) A mitochondrial NADH-dependent fumarate reductase involved in the production of succinate excreted by procyclic Trypanosoma brucei. J Biol Chem 280(17):16559–16570

    CAS  Google Scholar 

  • de Souza W, Atlas M, Rodrigues J (2009) Particularities of mitochondrial structure in parasitic protists (Apicomplexa and Kinetoplastida). Int J Biochem Cell Biol 41:2069–2080

    Google Scholar 

  • Duarte M, Mota N, Pinto L, Videira A (1998) Inactivation of the gene coding for the 30.4-kDa subunit of respiratory chain. NADH dehydrogenase: is the enzyme essential for Neurospora? Mol Gen Genet 257(3):368–375

    CAS  Google Scholar 

  • Duarte M, Videira A (2007) Mitochondrial NAD(P)H dehydrogenases in filamentous fungi. González Siso MI (ed), Complex I and alternative dehydrogenases: Transworld Research Network

  • Duarte M, Videira A (2000) Respiratory chain complex I is essential for sexual development in Neurospora and binding of iron sulfur clusters are required for enzyme assembly. Genetics 156(2):607–615

    CAS  Google Scholar 

  • Dudkina NV, Eubel H, Keegstra W, Boekema EJ, Braun HP (2005) Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. Proc Natl Acad Sci U S A 102(9):3225–3229

    CAS  Google Scholar 

  • Fang J, Beattie DS (2003a) External alternative NADH dehydrogenase of Saccharomyces cerevisiae: a potential source of superoxide. Free Radic Biol Med 34(4):478–488

    CAS  Google Scholar 

  • Fang J, Beattie DS (2003b) Identification of a gene encoding a 54 kDa alternative NADH dehydrogenase in Trypanosoma brucei. Mol Biochem Parasitol 127(1):73–77

    CAS  Google Scholar 

  • Fang J, Beattie DS (2002) Rotenone-insensitive NADH dehydrogenase is a potential source of superoxide in procyclic Trypanosoma brucei mitochondria. Mol Biochem Parasitol 123(2):135–142

    CAS  Google Scholar 

  • Fang J, Wang Y, Beattie DS (2001) Isolation and characterization of complex I, rotenone-sensitive NADH: ubiquinone oxidoreductase, from the procyclic forms of Trypanosoma brucei. Eur J Biochem 268(10):3075–3082

    CAS  Google Scholar 

  • Fecke W, Sled VD, Ohnishi T, Weiss H (1994) Disruption of the gene encoding the NADH-binding subunit of NADH: ubiquinone oxidoreductase in Neurospora crassa. Formation of a partially assembled enzyme without FMN and the iron-sulphur cluster N-3. Eur J Biochem 220(2):551–558

    CAS  Google Scholar 

  • Feng Y, Li W, Li J, Wang J, Ge J et al (2012) Structural insight into the type-II mitochondrial NADH dehydrogenases. Nature 491(7424):478–482

    CAS  Google Scholar 

  • Fisher N, Bray PG, Ward SA, Biagini GA (2007) The malaria parasite type II NADH:quinone oxidoreductase: an alternative enzyme for an alternative lifestyle. Trends Parasitol 23(7):305–310

    CAS  Google Scholar 

  • Galkin A, Meyer B, Wittig I, Karas M, Schagger H et al (2008) Identification of the mitochondrial ND3 subunit as a structural component involved in the active/deactive enzyme transition of respiratory complex I. J Biol Chem 283(30):20907–20913

    CAS  Google Scholar 

  • Gardner MJ, Hall N, Fung E, White O, Berriman M et al (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419(6906):498–511

    CAS  Google Scholar 

  • Gonzalez-Halphen D, Maslov DA (2004) NADH-ubiquinone oxidoreductase activity in the kinetoplasts of the plant trypanosomatid Phytomonas serpens. Parasitol Res 92(4):341–346

    Google Scholar 

  • Gray MW, Lang BF, Cedergren R, Golding GB, Lemieux C et al (1998) Genome structure and gene content in protist mitochondrial DNAs. Nucleic Acids Res 26(4):865–878

    CAS  Google Scholar 

  • Guarani V, Paulo J, Zhai B, Huttlin EL, Gygi SP et al (2014) TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex. Mol Cell Biol 34(5):847–861

    CAS  Google Scholar 

  • Guler JL, Kriegova E, Smith TK, Lukes J, Englund PT (2008) Mitochondrial fatty acid synthesis is required for normal mitochondrial morphology and function in Trypanosoma brucei. Mol Microbiol 67(5):1125–1142

    CAS  Google Scholar 

  • Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069

    CAS  Google Scholar 

  • Hernandez FR, Turrens JF (1998) Rotenone at high concentrations inhibits NADH-fumarate reductase and the mitochondrial respiratory chain of Trypanosoma brucei and T. cruzi. Mol Biochem Parasitol 93(1):135–137

    CAS  Google Scholar 

  • Horvath A, Horakova E, Dunajcikova P, Verner Z, Pravdova E et al (2005) Downregulation of the nuclear-encoded subunits of the complexes III and IV disrupts their respective complexes but not complex I in procyclic Trypanosoma brucei. Mol Microbiol 58(1):116–130

    CAS  Google Scholar 

  • Iwata M, Lee Y, Yamashita T, Yagi T, Iwata S et al (2012) The structure of the yeast NADH dehydrogenase (Ndi1) reveals overlapping binding sites for water- and lipid-soluble substrates. Proc Natl Acad Sci U S A 109(38):15247–15252

    CAS  Google Scholar 

  • Jasmer DP, Feagin JE, Stuart K (1985) Diverse patterns of expression of the cytochrome c oxidase subunit I gene and unassigned reading frames 4 and 5 during the life cycle of Trypanosoma brucei. Mol Cell Biol 5(11):3041–3047

    CAS  Google Scholar 

  • Kerscher SJ, Okun JG, Brandt U (1999) A single external enzyme confers alternative NADH:ubiquinone oxidoreductase activity in Yarrowia lipolytica. J Cell Sci 112(Pt 14):2347–2354

    CAS  Google Scholar 

  • Krause F, Scheckhuber CQ, Werner A, Rexroth S, Reifschneider NH et al (2006) OXPHOS Supercomplexes: respiration and life-span control in the aging model Podospora anserina. Ann N Y Acad Sci 1067:106–115

    CAS  Google Scholar 

  • Krause F, Scheckhuber CQ, Werner A, Rexroth S, Reifschneider NH et al (2004) Supramolecular organization of cytochrome c oxidase- and alternative oxidase-dependent respiratory chains in the filamentous fungus Podospora anserina. J Biol Chem 279(25):26453–26461

    CAS  Google Scholar 

  • Lazarou M, McKenzie M, Ohtake A, Thorburn DR, Ryan MT (2007) Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded subunits into complex I. Mol Cell Biol 27(12):4228–4237

    CAS  Google Scholar 

  • Lin SS, Gross U, Bohne W (2011) Two internal type II NADH dehydrogenases of Toxoplasma gondii are both required for optimal tachyzoite growth. Mol Microbiol 82(1):209–221

    CAS  Google Scholar 

  • Marques I, Dencher NA, Videira A, Krause F (2007) Supramolecular organization of the respiratory chain in Neurospora crassa mitochondria. Eukaryot Cell 6(12):2391–2405

    CAS  Google Scholar 

  • Marques I, Duarte M, Assuncao J, Ushakova AV, Videira A (2005) Composition of complex I from Neurospora crassa and disruption of two “accessory” subunits. Biochim Biophys Acta 1707(2–3):211–220

    CAS  Google Scholar 

  • Maslov DA (2010) Complete set of mitochondrial pan-edited mRNAs in Leishmania mexicana amazonensis LV78. Mol Biochem Parasitol 173(2):107–114

    CAS  Google Scholar 

  • Maslov DA, Zíková A, Kyselová I, Lukes J (2002) A putative novel nuclear-encoded subunit of the cytochrome c oxidase complex in trypanosomatids. Mol Biochem Parasitol 125:113–125

    CAS  Google Scholar 

  • Mathiesen C, Hagerhall C (2002) Transmembrane topology of the NuoL, M and N subunits of NADH:quinone oxidoreductase and their homologues among membrane-bound hydrogenases and bona fide antiporters. Biochim Biophys Acta 1556(2–3):121–132

    CAS  Google Scholar 

  • Melo AM, Bandeiras TM, Teixeira M (2004) New insights into type II NAD(P)H:quinone oxidoreductases. Microbiol Mol Biol Rev 68(4):603–616

    CAS  Google Scholar 

  • Mimaki M, Wang X, McKenzie M, Thorburn DR, Ryan MT (2012) Understanding mitochondrial complex I assembly in health and disease. Biochim Biophys Acta 1817(6):851–862

    CAS  Google Scholar 

  • Mitchell P, Moyle J (1967) Chemiosmotic hypothesis of oxidative phosphorylation. Nature 213(5072):137–139

    CAS  Google Scholar 

  • Moller IM (2002) A new dawn for plant mitochondrial NAD(P)H dehydrogenases. Trends Plant Sci 7(6):235–237

    CAS  Google Scholar 

  • Moyses DN, Barrabin H (2004) Rotenone-sensitive mitochondrial potential in Phytomonas serpens: electrophoretic Ca(2+) accumulation. Biochim Biophys Acta 1656(2–3):96–103

    Google Scholar 

  • Nebohacova M, Kim CE, Simpson L, Maslov DA (2009) RNA editing and mitochondrial activity in promastigotes and amastigotes of Leishmania donovani. Int J Parasitol 39(6):635–644

    CAS  Google Scholar 

  • Nijtmans LG, Henderson NS, Holt IJ (2002) Blue Native electrophoresis to study mitochondrial and other protein complexes. Methods 26(4):327–334

    CAS  Google Scholar 

  • Njogu RM, Whittaker CJ, Hill GC (1980) Evidence for a branched electron transport chain in Trypanosoma brucei. Mol Biochem Parasitol 1(1):13–29

    CAS  Google Scholar 

  • Nouws J, Nijtmans L, Houten SM, van den Brand M, Huynen M et al (2010) Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative phosphorylation complex I. Cell Metab 12(3):283–294

    CAS  Google Scholar 

  • Ogilvie I, Kennaway NG, Shoubridge EA (2005) A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J Clin Invest 115(10):2784–2792

    CAS  Google Scholar 

  • Ohnishi T, Kawaguchi K, Hagihara B (1966) Preparation and some properties of yeast mitochondria. J Biol Chem 241(8):1797–1806

    CAS  Google Scholar 

  • Opperdoes FR, Michels PA (2008) Complex I of Trypanosomatidae: does it exist? Trends Parasitol 24(7):310–317

    CAS  Google Scholar 

  • Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB et al (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134(1):112–123

    CAS  Google Scholar 

  • Pagniez-Mammeri H, Rak M, Legrand A, Benit P, Rustin P et al (2012) Mitochondrial complex I deficiency of nuclear origin II. Non-structural genes. Mol Genet Metab 105(2):173–179

    CAS  Google Scholar 

  • Panigrahi AK, Zikova A, Dalley RA, Acestor N, Ogata Y et al (2008) Mitochondrial complexes in Trypanosoma brucei: a novel complex and a unique oxidoreductase complex. Mol Cell Proteomics 7(3):534–545

    CAS  Google Scholar 

  • Papa S, Rasmo DD, Technikova-Dobrova Z, Panelli D, Signorile A et al (2012) Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases. FEBS Lett 586(5):568–577

    CAS  Google Scholar 

  • Peacock CS, Seeger K, Harris D, Murphy L, Ruiz JC et al (2007) Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nat Genet 39(7):839–847

    CAS  Google Scholar 

  • Pereira B, Videira A, Duarte M (2013) Novel insights into the role of Neurospora crassa NDUFAF2, an evolutionarily conserved mitochondrial complex I assembly factor. Mol Cell Biol 33(13):2623–2634

    CAS  Google Scholar 

  • Perez E, Lapaille M, Degand H, Cilibrasi L, Villavicencio-Queijeiro A et al (2014) The mitochondrial respiratory chain of the secondary green alga Euglena gracilis shares many additional subunits with parasitic Trypanosomatidae. Mitochondrion S1567–7249(14):00015–4

    Google Scholar 

  • Rasmusson AG, Soole KL, Elthon TE (2004) Alternative NAD(P)H dehydrogenases of plant mitochondria. Annu Rev Plant Biol 55:23–39

    CAS  Google Scholar 

  • Rhein VF, Carroll J, Ding S, Fearnley IM, Walker JE (2013) NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I. J Biol Chem 288(46):33016–33026

    CAS  Google Scholar 

  • Roberts PG, Hirst J (2012) The deactive form of respiratory complex. I from mammalian mitochondria is a Na+/H + antiporter. J Biol Chem 287(41):34743–34751

    CAS  Google Scholar 

  • Runswick MJ, Fearnley IM, Skehel JM, Walker JE (1991) Presence of an acyl carrier protein in NADH:ubiquinone oxidoreductase from bovine heart mitochondria. FEBS Lett 286(1–2):121–124

    CAS  Google Scholar 

  • Saada A, Vogel RO, Hoefs SJ, van den Brand MA, Wessels HJ et al (2009) Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease. Am J Hum Genet 84(6):718–727

    CAS  Google Scholar 

  • Santhamma KR, Bhaduri A (1995) Characterization of the respiratory chain of Leishmania donovani promastigotes. Mol Biochem Parasitol 75(1):43–53

    CAS  Google Scholar 

  • Schagger H, Pfeiffer K (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 19(8):1777–1783

    CAS  Google Scholar 

  • Schnaufer A, Domingo GJ, Stuart K (2002) Natural and induced dyskinetoplastic trypanosomatids: how to live without mitochondrial DNA. Int J Parasitol 32(9):1071–1084

    CAS  Google Scholar 

  • Schneider R, Massow M, Lisowsky T, Weiss H (1995) Different respiratory-defective phenotypes of Neurospora crassa and Saccharomyces cerevisiae after inactivation of the gene encoding the mitochondrial acyl carrier protein. Curr Genet 29(1):10–17

    CAS  Google Scholar 

  • Schulte U, Haupt V, Abelmann A, Fecke W, Brors B et al (1999) A reductase/isomerase subunit of mitochondrial NADH:ubiquinone oxidoreductase (complex I) carries an NADPH and is involved in the biogenesis of the complex. J Mol Biol 292(3):569–580

    CAS  Google Scholar 

  • Seo BB, Nakamaru-Ogiso E, Flotte TR, Matsuno-Yagi A, Yagi T (2006) In vivo complementation of complex I by the yeast Ndi1 enzyme. Possible application for treatment of Parkinson disease. J Biol Chem 281(20):14250–14255

    CAS  Google Scholar 

  • Simpson L, Wang SH, Thiemann OH, Alfonzo JD, Maslov DA et al (1998) U-insertion/deletion Edited Sequence Database. Nucleic Acids Res 26(1):170–176

    CAS  Google Scholar 

  • Smeitink JA, van den Heuvel LW, Koopman WJ, Nijtmans LG, Ugalde C et al (2004) Cell biological consequences of mitochondrial NADH: ubiquinone oxidoreductase deficiency. Curr Neurovasc Res 1(1):29–40

    CAS  Google Scholar 

  • Sousa PM, Videira MA, Bohn A, Hood BL, Conrads TP et al (2012) The aerobic respiratory chain of Escherichia coli: from genes to supercomplexes. Microbiology 158(Pt 9):2408–2418

    CAS  Google Scholar 

  • Souza AE, Myler PJ, Stuart K (1992) Maxicircle CR1 transcripts of Trypanosoma brucei are edited and developmentally regulated and encode a putative iron-sulfur protein homologous to an NADH dehydrogenase subunit. Mol Cell Biol 12(5):2100–2107

    CAS  Google Scholar 

  • Stephens JL, Lee SH, Paul KS, Englund PT (2007) Mitochondrial fatty acid synthesis in Trypanosoma brucei. J Biol Chem 282(7):4427–4436

    CAS  Google Scholar 

  • Stroh A, Anderka O, Pfeiffer K, Yagi T, Finel M et al (2004) Assembly of respiratory complexes I, III, and IV into NADH oxidase supercomplex stabilizes complex I in Paracoccus denitrificans. J Biol Chem 279(6):5000–5007

    CAS  Google Scholar 

  • Stroud DA, Formosa LE, Wijeyeratne XW, Nguyen TN, Ryan MT (2013) Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I. J Biol Chem 288(3):1685–1690

    CAS  Google Scholar 

  • Sugiana C, Pagliarini DJ, McKenzie M, Kirby DM, Salemi R et al (2008) Mutation of C20orf7 disrupts complex I assembly and causes lethal neonatal mitochondrial disease. Am J Hum Genet 83(4):468–478

    CAS  Google Scholar 

  • Surve S, Heestand M, Panicucci B, Schnaufer A, Parsons M (2012) Enigmatic presence of mitochondrial complex I in Trypanosoma brucei bloodstream forms. Eukaryot Cell 11(2):183–193

    CAS  Google Scholar 

  • Thiemann OH, Maslov DA, Simpson L (1994) Disruption of RNA editing in Leishmania tarentolae by the loss of minicircle-encoded guide RNA genes. EMBO J 13(23):5689–5700

    CAS  Google Scholar 

  • Tielens AG, van Hellemond JJ (2009) Surprising variety in energy metabolism within Trypanosomatidae. Trends Parasitol 25(10):482–490

    Google Scholar 

  • Tocilescu MA, Zickermann V, Zwicker K, Brandt U (2010) Quinone binding and reduction by respiratory complex I. Biochim Biophys Acta 1797(12):1883–1890

    CAS  Google Scholar 

  • Tomas AM, Castro H (2013) Redox metabolism in mitochondria of trypanosomatids. Antioxid Redox Signal 19(7):696–707

    CAS  Google Scholar 

  • Torija P, Vicente JJ, Rodrigues TB, Robles A, Cerdan S et al (2006) Functional genomics in Dictyostelium: MidA, a new conserved protein, is required for mitochondrial function and development. J Cell Sci 119(Pt 6):1154–1164

    CAS  Google Scholar 

  • Turrens JF (1987) Possible role of the NADH-fumarate reductase in superoxide anion and hydrogen peroxide production in Trypanosoma brucei. Mol Biochem Parasitol 25(1):55–60

    CAS  Google Scholar 

  • Verner Z, Cermakova P, Skodova I, Kovacova B, Lukes J et al (2014) Comparative analysis of respiratory chain and oxidative phosphorylation in Leishmania tarentolae, Crithidia fasciculata, Phytomonas serpens and procyclic stage of Trypanosoma brucei. Mol Biochem Parasitol 193(1):55–65

    CAS  Google Scholar 

  • Verner Z, Cermakova P, Skodova I, Kriegova E, Horvath A et al (2011) Complex I (NADH:ubiquinone oxidoreductase) is active in but non-essential for procyclic Trypanosoma brucei. Mol Biochem Parasitol 175(2):196–200

    CAS  Google Scholar 

  • Verner Z, Skodova I, Polakova S, Durisova-Benkovicova V, Horvath A et al (2013) Alternative NADH dehydrogenase (NDH2): intermembrane-space-facing counterpart of mitochondrial complex I in the procyclic Trypanosoma brucei. Parasitol 140(3):328–337

    CAS  Google Scholar 

  • Walker JE (1992) The NADH:ubiquinone oxidoreductase (complex I) of respiratory chains. Q Rev Biophys 25:253–324

    CAS  Google Scholar 

  • Wydro MM, Sharma P, Foster JM, Bych K, Meier EH et al (2013) The evolutionarily conserved iron-sulfur protein INDH is required for complex I assembly and mitochondrial translation in Arabidopsis. Plant Cell 25:4014–4027

    CAS  Google Scholar 

  • Yagi T, Matsuno-Yagi A (2003) The proton-translocating NADH-quinone oxidoreductase in the respiratory chain: the secret unlocked. Biochemistry 42(8):2266–2274

    CAS  Google Scholar 

  • Yip CY, Harbour ME, Jayawardena K, Fearnley IM, Sazanov LA (2011) Evolution of respiratory complex I: “supernumerary” subunits are present in the alpha-proteobacterial enzyme. J Biol Chem 286(7):5023–5033

    CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Fundação para a Ciência e a Tecnologia, Portugal for financial support [Fundo Europeu de Desenvolvimento Regional-FEDER funds through the Operational Competitiveness Program—COMPETE and National Funds through FCT FCOMP-01-0124-FEDER-009506 (PTDC/CVT/100090/2008)]. We would like to thank Patrícia Carneiro for critically reading the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Margarida Duarte.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duarte, M., Tomás, A.M. The mitochondrial complex I of trypanosomatids - an overview of current knowledge. J Bioenerg Biomembr 46, 299–311 (2014). https://doi.org/10.1007/s10863-014-9556-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-014-9556-x

Keywords

Navigation