Publication: Bromodomain inhibitors correct bioenergetic deficiency caused by mitochondrial disease complex I mutations
Bromodomain inhibitors correct bioenergetic deficiency caused by mitochondrial disease complex I mutations
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Barrow, J. J., Balsa, E., Verdeguer, F., Tavares, C. D. J., Soustek, M. S., Hollingsworth, L. R., Jedrychowski, M., Vogel, R., Paulo, J. A., Smeitink, J., Gygi, S. P., Doench, J., Root, D. E., & Puigserver, P. (2016). Bromodomain inhibitors correct bioenergetic deficiency caused by mitochondrial disease complex I mutations. Molecular Cell, 64(1), 163–175. https://doi.org/10.1016/j.molcel.2016.08.023
Abstract
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Abstract
Mitochondrial diseases comprise a heterogeneous group of genetically inherited disorders that cause failures in energetic and metabolic function. Boosting residual oxidative phosphorylation (OXPHOS) activity can partially correct these failures. Herein, using a high-throughput chemical screen, we identified the bromodomain inhibitor I-BET 525762A as one of the top hits that increases COX5a protein levels in complex I (CI) mutant cybrid cells. In parallel, bromodomain-containing protein 4 (BRD4), a target of I-BET 525762A, was identifi
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- Barrow, Joeva J
- Balsa, Eduardo
- Tavares, Clint D J
- Soustek, Meghan S
- Hollingsworth, Louis R
- Jedrychowski, Mark
- Vogel, Rutger
- Paulo, Joao A
- Smeitink, Jan
- Gygi, Steve P
- Doench, John
- Root, David E
- Puigserver, Pere
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Barrow, J. J., Balsa, E., Verdeguer, F., Tavares, C. D. J., Soustek, M. S., Hollingsworth, L. R., Jedrychowski, M., Vogel, R., Paulo, J. A., Smeitink, J., Gygi, S. P., Doench, J., Root, D. E., & Puigserver, P. (2016). Bromodomain inhibitors correct bioenergetic deficiency caused by mitochondrial disease complex I mutations. Molecular Cell, 64(1), 163–175. https://doi.org/10.1016/j.molcel.2016.08.023
