Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration.
An increasing body of evidence suggests that high intracellular free zinc promotes neuronal death by inhibiting cellular energy production. A number of targets have been postulated, including complexes of the mitochondrial electron transport chain, components of the tricarboxylic acid cycle, and enzymes of glycolysis. Consequences of cellular zinc overload may include increased cellular reactive oxygen species (ROS) production, loss of mitochondrial membrane potential, and reduced cellular ATP levels. Additionally, zinc toxicity might involve zinc uptake by mitochondria and zinc induction of mitochondrial permeability transition. The present review discusses these processes with special emphasis on their potential involvement in brain injury.
Dineley
Kirk E
KE
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Votyakova
Tatyana V
TV
Reynolds
Ian J
IJ
D002952:Citric Acid Cycle / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015032:Zinc / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*
D017382:Reactive Oxygen Species; D008668:Metallothionein; D015032:Zinc