Experts and Doctors on electron transport complex i in Nijmegen, Gelderland, Netherlands


Locale: Nijmegen, Gelderland, Netherlands
Topic: electron transport complex i

Top Publications

  1. Smits P, Mattijssen S, Morava E, van den Brand M, van den Brandt F, Wijburg F, et al. Functional consequences of mitochondrial tRNA Trp and tRNA Arg mutations causing combined OXPHOS defects. Eur J Hum Genet. 2010;18:324-9 pubmed publisher
    ..Our results show that these tRNA(Trp) and tRNA(Arg) mutations cause the combined OXPHOS deficiencies in the patients, adding to the still expanding group of pathogenic mitochondrial tRNA mutations. ..
  2. Manjeri G, Rodenburg R, Blanchet L, Roelofs S, Nijtmans L, Smeitink J, et al. Increased mitochondrial ATP production capacity in brain of healthy mice and a mouse model of isolated complex I deficiency after isoflurane anesthesia. J Inherit Metab Dis. 2016;39:59-65 pubmed publisher
    ..01), respectively. Together these findings indicate that isoflurane anesthesia interferes positively rather than negatively with the ability of CI-deficient mice brain mitochondria to convert their main substrate pyruvate into ATP. ..
  3. Dieteren C, Willems P, Swarts H, Fransen J, Smeitink J, Koopman W, et al. Defective mitochondrial translation differently affects the live cell dynamics of complex I subunits. Biochim Biophys Acta. 2011;1807:1624-33 pubmed publisher
    ..Our results show that the protein interactions of CI subunits and assembly factors are differently altered when mitochondrial translation is defective. ..
  4. Valsecchi F, Koopman W, Manjeri G, Rodenburg R, Smeitink J, Willems P. Complex I disorders: causes, mechanisms, and development of treatment strategies at the cellular level. Dev Disabil Res Rev. 2010;16:175-82 pubmed publisher
    ..There are currently no rational treatment strategies. Here, we present an overview of the genetic origins and cellular consequences of this deficiency and discuss how these insights might aid future development of treatment strategies. ..
  5. Nouws J, Nijtmans L, Smeitink J, Vogel R. Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options. Brain. 2012;135:12-22 pubmed publisher
    ..In this review, we will address whether the functions of these chaperones point towards a general molecular mechanism of disease and whether this enables us to design a treatment for complex I deficiency. ..
  6. Forkink M, Smeitink J, Brock R, Willems P, Koopman W. Detection and manipulation of mitochondrial reactive oxygen species in mammalian cells. Biochim Biophys Acta. 2010;1797:1034-44 pubmed publisher
    ..Finally, approaches involving targeted pro- and antioxidants are presented, which allow the local manipulation of ROS levels. ..
  7. Blanchet L, Buydens M, Smeitink J, Willems P, Koopman W. Isolated mitochondrial complex I deficiency: explorative data analysis of patient cell parameters. Curr Pharm Des. 2011;17:4023-33 pubmed
    ..This information not only contributes to our understanding of the pathophysiological mechanism of CI and mitochondrial deficiency but also suggests possible targets for cellular intervention strategies. ..
  8. Distelmaier F, Visch H, Smeitink J, Mayatepek E, Koopman W, Willems P. The antioxidant Trolox restores mitochondrial membrane potential and Ca2+ -stimulated ATP production in human complex I deficiency. J Mol Med (Berl). 2009;87:515-22 pubmed publisher
    ..Together, these results provide evidence for an integral role of increased ROS levels in complex I deficiency and point to the potential therapeutic value of antioxidant treatment. ..
  9. Koene S, Rodenburg R, van der Knaap M, Willemsen M, Sperl W, Laugel V, et al. Natural disease course and genotype-phenotype correlations in Complex I deficiency caused by nuclear gene defects: what we learned from 130 cases. J Inherit Metab Dis. 2012;35:737-47 pubmed publisher
    ..No clear genotype-phenotype correlations were observed, however defects in some genes seem to be associated with a better or poorer prognosis, cardiomyopathy, Leigh syndrome or brainstem lesions. ..

More Information


  1. Janssen A, Trijbels F, Sengers R, Smeitink J, van den Heuvel L, Wintjes L, et al. Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin Chem. 2007;53:729-34 pubmed
    ..This spectrophotometric assay is reproducible, sensitive, and specific for complex I activity because of its high rotenone sensitivity, and it can be applied successfully to the diagnosis of complex I deficiencies. ..
  2. Farhoud M, Nijtmans L, Wanders R, Wessels H, Lasonder E, Janssen A, et al. Impaired ubiquitin-proteasome-mediated PGC-1? protein turnover and induced mitochondrial biogenesis secondary to complex-I deficiency. Proteomics. 2012;12:1349-62 pubmed publisher
    ..Thus, mitochondrial biogenesis, which lays at the heart of the homeostatic control of energy metabolism, can be deregulated by secondary impairments of the protein turnover machinery. ..
  3. Willems P, Smeitink J, Koopman W. Mitochondrial dynamics in human NADH:ubiquinone oxidoreductase deficiency. Int J Biochem Cell Biol. 2009;41:1773-82 pubmed publisher
    ..This suggests that the amount of mitochondria, and not their shape, is important for Ca(2+)-induced stimulation of mitochondrial ATP generation to feed cytosolic ATP-demanding processes. ..
  4. Valsecchi F, Grefte S, Roestenberg P, Joosten Wagenaars J, Smeitink J, Willems P, et al. Primary fibroblasts of NDUFS4(-/-) mice display increased ROS levels and aberrant mitochondrial morphology. Mitochondrion. 2013;13:436-43 pubmed publisher
    ..Oxidation of the ROS sensor hydroethidium was increased and mitochondria were less branched and/or shorter in NDUFS4(-/-) fibroblasts. We discuss the relevance of these findings with respect to previous results and therapy development. ..
  5. Valsecchi F, Monge C, Forkink M, de Groof A, Benard G, Rossignol R, et al. Metabolic consequences of NDUFS4 gene deletion in immortalized mouse embryonic fibroblasts. Biochim Biophys Acta. 2012;1817:1925-36 pubmed publisher
    ..This article is part of a special issue entitled: 17th European Bioenergetics Conference (EBEC 2012). ..
  6. Hoefs S, Rodenburg R, Smeitink J, van den Heuvel L. Molecular base of biochemical complex I deficiency. Mitochondrion. 2012;12:520-32 pubmed publisher
  7. Breuer M, Willems P, Smeitink J, Koopman W, Nooteboom M. Cellular and animal models for mitochondrial complex I deficiency: a focus on the NDUFS4 subunit. IUBMB Life. 2013;65:202-8 pubmed publisher
    ..In this review, we discuss these models and their validity for studying human CI deficiency. ..
  8. Hoefs S, Skjeldal O, Rodenburg R, Nedregaard B, van Kaauwen E, Spiekerk├Âtter U, et al. Novel mutations in the NDUFS1 gene cause low residual activities in human complex I deficiencies. Mol Genet Metab. 2010;100:251-6 pubmed publisher
    ..In addition, a disturbed assembly pattern was observed. These results suggest that NDUFS1 is a prime candidate to screen for disease-causing mutations in patients with a very low residual complex I activity in cultured fibroblasts. ..
  9. Szklarczyk R, Wanschers B, Nabuurs S, Nouws J, Nijtmans L, Huynen M. NDUFB7 and NDUFA8 are located at the intermembrane surface of complex I. FEBS Lett. 2011;585:737-43 pubmed publisher
    ..We experimentally confirm the localization of the latter two, while our data are consistent with disulfide bridges in NDUFA8. We propose these subunits stabilize the membrane domain of complex I. ..
  10. Hoefs S, van Spronsen F, Lenssen E, Nijtmans L, Rodenburg R, Smeitink J, et al. NDUFA10 mutations cause complex I deficiency in a patient with Leigh disease. Eur J Hum Genet. 2011;19:270-4 pubmed publisher
    ..These results indicate that NDUFA10 is a novel candidate gene to screen for disease-causing mutations in patients with complex I deficiency. ..
  11. Vogel R, van den Brand M, Rodenburg R, van den Heuvel L, Tsuneoka M, Smeitink J, et al. Investigation of the complex I assembly chaperones B17.2L and NDUFAF1 in a cohort of CI deficient patients. Mol Genet Metab. 2007;91:176-82 pubmed
    ..These findings illustrate the difference in mechanism between B17.2L and NDUFAF1 and suggest that the involvement of NDUFAF1 in the assembly process could be indirect rather than direct via the binding to assembly intermediates. ..
  12. Ngu L, Nijtmans L, Distelmaier F, Venselaar H, van Emst de Vries S, van den Brand M, et al. A catalytic defect in mitochondrial respiratory chain complex I due to a mutation in NDUFS2 in a patient with Leigh syndrome. Biochim Biophys Acta. 2012;1822:168-75 pubmed publisher
    ..We propose that the mutation interferes with the reduction of coenzyme Q or with the coupling of coenzyme Q reduction with the conformational changes involved in proton pumping of complex I. ..
  13. de Coo R, Buddiger P, Smeets H, van Oost B. Molecular cloning and characterization of the human mitochondrial NADH:oxidoreductase 10-kDa gene (NDUFV3). Genomics. 1997;45:434-7 pubmed
    ..Northern blot analysis showed that the NDUFV3 gene is ubiquitously expressed. The NDUFV3 gene was assigned by FISH to a single location on chromosome 21q22.3 and might contribute to the Down syndrome phenotype. ..
  14. Koopman W, Nijtmans L, Dieteren C, Roestenberg P, Valsecchi F, Smeitink J, et al. Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation. Antioxid Redox Signal. 2010;12:1431-70 pubmed publisher
  15. Wessels H, Vogel R, Van Den Heuvel L, Smeitink J, Rodenburg R, Nijtmans L, et al. LC-MS/MS as an alternative for SDS-PAGE in blue native analysis of protein complexes. Proteomics. 2009;9:4221-8 pubmed publisher
  16. Hoefs S, Dieteren C, Rodenburg R, Naess K, Bruhn H, Wibom R, et al. Baculovirus complementation restores a novel NDUFAF2 mutation causing complex I deficiency. Hum Mutat. 2009;30:E728-36 pubmed publisher
    ..Therefore, the homozygous substitution in NDUFAF2 is the disease-causing mutation, which results in a complex I deficiency in the fibroblasts of the patient. ..
  17. Dieteren C, Willems P, Vogel R, Swarts H, Fransen J, Roepman R, et al. Subunits of mitochondrial complex I exist as part of matrix- and membrane-associated subcomplexes in living cells. J Biol Chem. 2008;283:34753-61 pubmed publisher
    ..Our results provide first time evidence for the existence of CI subassemblies in mitochondria of living cells. ..
  18. Ruiter E, Siers M, van den Elzen C, van Engelen B, Smeitink J, Rodenburg R, et al. The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White. Eur J Hum Genet. 2007;15:155-61 pubmed
    ..In addition, we confirmed that the adjacent m.13514A > G mutation is a rare cause of LS or MELAS since no cases with this transition were found. ..
  19. Janssen R, Nijtmans L, van den Heuvel L, Smeitink J. Mitochondrial complex I: structure, function and pathology. J Inherit Metab Dis. 2006;29:499-515 pubmed
    ..Unravelling the intricate mechanisms underlying the functioning of this membrane-bound enzyme complex in health and disease will pave the way for developing adequate diagnostic procedures and advanced therapeutic treatment strategies. ..
  20. Ugalde C, Janssen R, van den Heuvel L, Smeitink J, Nijtmans L. Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency. Hum Mol Genet. 2004;13:659-67 pubmed
    ..This will help us to point more selectively to candidate genes for pathogenic mutations that could lead to an isolated complex I defect. ..