TY - JOUR
T1 - Cell biological consequences of mitochondrial NADH
T2 - ubiquinone oxidoreductase deficiency
AU - Smeitink, Jan A.M.
AU - van den Heuvel, Lambert W.P.J.
AU - Koopman, Werner J.H.
AU - Nijtmans, Leo G.J.
AU - Ugalde, Cristina
AU - Willems, Peter H.G.M.
PY - 2004/1
Y1 - 2004/1
N2 - 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.
AB - 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.
U2 - 10.2174/1567202043480224
DO - 10.2174/1567202043480224
M3 - Article
C2 - 16181064
AN - SCOPUS:3042856987
SN - 1567-2026
VL - 1
SP - 29
EP - 40
JO - Current Neurovascular Research
JF - Current Neurovascular Research
IS - 1
ER -