2. Academic Validation
  3. Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh syndrome

Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh syndrome

  • Mol Genet Metab. 2007 Jan;90(1):10-4. doi: 10.1016/j.ymgme.2006.08.003.
Cristina Ugalde 1,  Reetta Hinttala,  Sharita Timal,  Roel Smeets,  Richard J T Rodenburg,  Johanna Uusimaa,  Lambert P van Heuvel,  Leo G J Nijtmans,  Kari Majamaa,  Jan A M Smeitink
Affiliations

Affiliation

  • 1 Nijmegen Center for Mitochondrial Disorders, Department of Pediatrics, Radboud University Nijmegen Medical Center, Geert Grooteplein 10, 6500 HB Nijmegen, The Netherlands.
PMID: 16996290 DOI: 10.1016/j.ymgme.2006.08.003
Abstract

We describe a novel mitochondrial ND2 mutation (T4681C) in a patient presenting with Leigh Syndrome. Biochemical analyses revealed a low isolated complex I activity in patient's fibroblasts, blood and skeletal muscle. Mutant transmitochondrial cybrid clones retained the specific complex I defect, demonstrating the mitochondrial genetic origin of the disease. The mutation leads to a L71P substitution at an evolutionary conserved amino acid stretch. By two-dimensional blue native electrophoresis (2D-BN-SDS-PAGE), decreased complex I levels were observed together with an accumulation of specific assembly intermediates, suggesting that the mutation disturbs the complex I assembly pathway.

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