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Gonzalez-Halphen, D; Ghelli, A; Iommarini, L; Carelli, V; Esposti, MD (2011)

MITOCHONDRIAL COMPLEX I AND CELL DEATH: A SEMI-AUTOMATIC SHOTGUN MODEL

CELL DEATH DIS 2():-
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Mitochondrial dysfunction often leads to cell death and disease. We can now draw correlations between the dysfunction of one of the most important mitochondrial enzymes, NADH: ubiquinone reductase or complex I, and its structural organization thanks to the recent advances in the X-ray structure of its bacterial homologs. The new structural information on bacterial complex I provide essential clues to finally understand how complex I may work. However, the same information remains difficult to interpret for many scientists working on mitochondrial complex I from different angles, especially in the field of cell death. Here, we present a novel way of interpreting the bacterial structural information in accessible terms. On the basis of the analogy to semi-automatic shotguns, we propose a novel functional model that incorporates recent structural information with previous evidence derived from studies on mitochondrial diseases, as well as functional bioenergetics. Cell Death and Disease 2011) 2, e222; doi: 10.1038/cddis.2011.107; published online 27 October 2011