OXPHOS complex I deficiency leads to transcriptional changes of the Nrf2-Keap1 pathway and selenoproteins.

Defective complex I (CI) is the most common type of oxidative phosphorylation (OXPHOS) disease in patients, with an incidence of 1 in 5,000 live births. Complex I deficiency can present in infancy or early adulthood and shows a wide variety of clinical manifestations, including Leigh syndrome, (cardio)myopathy, hypotonia, stroke, ataxia and lactic acidosis. A number of critical processes and factors, like superoxide production, calcium homeostasis, mitochondrial membrane potential and mitochondrial morphology, are known to be involved in clinical CI deficiency, but not all factors are yet known and a complete picture is lacking.

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Voets AM, Huigsloot M, Lindsey PJ, Leenders AM, Koopman WJ, Willems PH, Rodenburg RJ, Smeitink JA, Smeets HJ