Mitochondrial complex I and cell death: a semi-automatic shotgun model.
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.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México DF, México.
D
D
Gonzalez-Halphen
A
A
Ghelli
L
L
Iommarini
V
V
Carelli
M D
MD
Esposti
D016923:Cell Death / Q000502:physiology; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D042967:Electron Transport Complex I