Iron and copper mitochondrial toxicities in rat brain

REPETTO, M; BOVERIS, A

Brain mitochondria: distribution and function

Nova

Año: 2020; p. 83 - 105

The natural history and the biological significance of the metals iron (Fe) and copper (Cu) are reviewed. They are part of essential prosthetic groups in proteins and enzymes in mammals. The two elements have active roles in the catalyzed reactions with mobilization of metal electrons during catalysis. Fe is in the active centers of hemoglobin, myoglobin and cytochrome oxidase, whereas Cu is in the active centers of superoxide dismutase-1 and of cytochrome oxidase. High levels of brain Fe and Cu are related to neurodegenerative diseases and cognitive disorders through oxidative stress and protein misfolding and aggregation. Increased in situ brain chemiluminescence indicates an oxidative stress produced by a free-radical mechanism that supports lipid peroxidation and protein oxidation. Haber-Weiss type reactions mediated by cytosolic Fe and Cu initiate the free-radical reactions. Experimental results on the effects of Fe and Cu overloads in brain oxidative metabolism, glutathione (GSH content), and the reduced and oxidized GSH ratio (GSH/GSSG) are included. Acute Cu overloads decreased state 3 oxygen uptake and respiratory control, impairing the mitochondrial function of adenosine triphosphate (ATP) formation.