Mitochondrial biochemistry


The main research topic addressed in the biochemistry group is the functional characterization of novel defects of the mitochondrial energy generating system. Nowadays most new genetic defects are identified by exome sequencing and often require further validation. For these validation studies, patients’ fibroblasts and myoblast cell lines are an important tool. The functioning of the mitochondrial ATP production machinery in these cells is examined by ATP production, pyruvate oxidation and oxygen consumption rate measurements, respiratory chain enzyme activity assays, immunohistochemical and Western blot analysis of various mitochondrial enzymes. In addition, a number array of additional tests and technology platforms are available in our center, including a proteomics/metabolomics facility and a microscopy facility. The results of these studies are essential for establishing a diagnosis in patients with new genetic defects and provide new insights in the ethiology of mitochondrial disorders.

Recent publications

  1. Mitochondrial complex I-linked disease. Rodenburg RJ. Biochim Biophys Acta. 2016 Feb 22. pii: S0005-2728(16)30031-7. doi: 10.1016/j.bbabio.2016.02.012. [Epub ahead of print] PubMed PMID: 26906428.

  2. A novel mitochondrial DNA m.7507A>G mutation is only pathogenic at high levels of heteroplasmy. McCann BJ, Tuppen HA, Küsters B, Lammens M, Smeitink JA, Taylor RW, Rodenburg  RJ, Wortmann SB. Neuromuscul Disord. 2015 Mar;25(3):262-7.

  3. Whole exome sequencing of suspected mitochondrial patients in clinical practice.Wortmann SB, Koolen DA, Smeitink JA, van den Heuvel L, Rodenburg RJ. J Inherit Metab Dis. 2015 Mar 4. [Epub ahead of print] PubMed PMID: 25735936. 

  4. SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Renkema GH, Wortmann SB, Smeets RJ,Venselaar H, Antoine M, Visser G, Ben-Omran T, van den Heuvel LP, Timmers HJ,Smeitink JA, Rodenburg RJ. Eur J Hum Genet. 2015 Feb;23(2):202-9.

  5. Mutations in COA6 cause cytochrome c oxidase deficiency and neonatal hypertrophic
    cardiomyopathy. Baertling F, A M van den Brand M, Hertecant JL, Al-Shamsi A, P van den Heuvel L, Distelmaier F, Mayatepek E, Smeitink JA, Nijtmans LG, Rodenburg RJ. Hum Mutat. 2015 Jan;36(1):34-8.

  6. A complex V ATP5A1 defect causes fatal neonatal mitochondrial encephalopathy. Jonckheere AI, Renkema GH, Bras M, van den Heuvel LP, Hoischen A, Gilissen C, Nabuurs SB, Huynen MA, de Vries MC, Smeitink JA, Rodenburg RJ. Brain. 2013 May;136(Pt 5):1544-54

  7. Mitochondrial ATP synthase: architecture, function and pathology. Jonckheere AI, Smeitink JA, Rodenburg RJ. J Inherit Metab Dis. 2012 Mar;35(2):211-25

  8. A mutation in C2orf64 causes impaired cytochrome c oxidase assembly and mitochondrial cardiomyopathy. Huigsloot M, Nijtmans LG, Szklarczyk R, Baars MJ, van den Brand MA, Hendriksfranssen MG, van den Heuvel LP, Smeitink JA, Huynen MA, Rodenburg RJ. Am J Hum Genet. 2011 Apr 8;88(4):488-93

  9. Biochemical diagnosis of mitochondrial disorders. Rodenburg RJ. J Inherit Metab Dis. 2011 Apr;34(2):283-92

  10. Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Janssen AJ, Trijbels FJ, Sengers RC, Smeitink JA, van den Heuvel LP, Wintjes LT, Stoltenborg-Hogenkamp BJ, Rodenburg RJ. Clin Chem. 2007 Apr;53(4):729-34