Transcriptional changes in oxphos complex i deficiency are related to anti-oxidant pathways and could explain the disturbed calcium homeostasis

A.M. Voets, M. Huigsloot, P.J. Lindsey, A.M. Leenders, W.J.H. Koopman, P. Willems, R. J. Rodenburg, J.A.M. Smeitink, H.J.M. Smeets*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Defective complex I (CI) is the most common type of oxidative phosphorylation disease, with an incidence of 1 in 5000 live births. Here, whole genome expression profiling of fibroblasts from CI deficient patients was performed to gain insight into the cell pathological mechanism. Our results suggest that patient fibroblasts responded to oxidative stress by Nrf2-mediated induction of the glutathione antioxidant system and Gadd45-mediated activation of the DNA damage response pathway. Furthermore, the observed reduced expression of selenoproteins, might explain the disturbed calcium homeostasis previously described for the patient fibroblasts and might be linked to endoplasmic reticulum stress. These results suggest that both glutathione and selenium metabolism are potentially therapeutic targets in CI deficiency. (c) 2011 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1161-1168
JournalBiochimica et Biophysica Acta-Molecular Basis of Disease
Issue number7
Publication statusPublished - 1 Jan 2012

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