Cell biological consequences of mitochondrial NADH: ubiquinone oxidoreductase deficiency

Jan A.M. Smeitink*, Lambert W.P.J. van den Heuvel, Werner J.H. Koopman, Leo G.J. Nijtmans, Cristina Ugalde, Peter H.G.M. Willems

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

54 Citations (Scopus)

Abstract

Human complex I (NADH:ubiquinone oxidoreductase; EC 1.6.5.3) is the first and largest multi-protein assembly of the mitochondrial oxidative phosphorylation (OXPHOS) system; the final biochemical cascade of events leading to the production of ATP. The complex consists of 46 subunits, 7 encoded by the mitochondrial DNA and the remainder by the nuclear genome. In recent years, numerous gene mutations leading to an isolated complex I deficiency have been characterized in both genomes. Disorders associated with complex I deficiency (OMIM 252010) mostly lead to multi-system disorders affecting brain, skeletal muscle and the heart. Of these, Leigh syndrome, a progressive fatal encephalopathy symmetrically affecting specific areas of the brain, brainstem and myelin, is the most frequently observed phenotype. Here, we review the current understanding of the cell biological consequences of isolated complex I deficiencies and propose further directions the field needs to take in order to develop rational treatment strategies for these devastating disorders.

Original languageEnglish
Pages (from-to)29-40
Number of pages12
JournalCurrent Neurovascular Research
Volume1
Issue number1
DOIs
Publication statusPublished - Jan 2004
Externally publishedYes

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