Complex I and energy thresholds in the brain.
Mitochondrial electron transport chain (ETC) deficiencies are thought to underlie defects in energy metabolism and have been implicated in the neurodegenerative process. In particular, reductions in complex I activities in Parkinson's disease are thought to cause bioenergetic dysfunction with subsequent degeneration of dopaminergic neurons. In terms of bioenergetics and assessing ETC-related problems in the brain, the presence of heterogeneous mitochondria has complicated matters as isolated non-synaptic mitochondria have different energy thresholds and flux control coefficients compared to isolated mitochondria of synaptic origin. The molecular mechanisms that underlie complex I deficiencies in the parkinsonian brain are unknown and are the source of intensive research. This review explores the relationship between complex I activity and energy metabolism in the brain as well as the nature of the complex I defect.
Pathak
Rashmi U
RU
School of Biochemistry and Immunology and Trinity College Institute of Neuroscience, Trinity College Dublin, Ireland.
Davey
Gavin P
GP
D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004579:Electron Transport; D042967:Electron Transport Complex I / Q000172:deficiency / Q000187:drug effects / Q000378:metabolism*; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D004734:Energy Metabolism; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010300:Parkinson Disease / Q000201:enzymology
D042963:Electron Transport Complex II; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; D005978:Glutathione