Hermes-Lima M, Castilho R F, Valle V G, Bechara E J, Vercesi A E
Departamento de Bioquímica, Universidade Estadual de Campinas, Brazil.
Biochim Biophys Acta. 1992 Dec 10;1180(2):201-6. doi: 10.1016/0925-4439(92)90069-y.
Swelling of isolated rat liver mitochondria is shown to be induced by metal-catalyzed 5-aminolevulinic acid (ALA) aerobic oxidation, a putative endogenous source of reactive oxygen species (ROS), at concentrations as low as 50-100 microM. In this concentration range, ALA is estimated to occur in the liver of acute intermittent porphyria patients. Removal of Ca2+ (10 microM) from the suspension of isolated rat liver mitochondria by added EGTA abolishes both the ALA-induced transmembrane-potential collapse and mitochondrial swelling. Prevention of the ALA-induced swelling by addition of ruthenium red prior to mitochondrial energization by succinate demonstrates the deleterious involvement of internal Ca2+. Addition of MgCl2 at concentrations higher than 2.5 mM, prevents the ALA-induced mitochondrial swelling, transmembrane potential collapse and Ca2+ efflux. This indicates that Mg2+ protects against the mitochondrial damage promoted by ALA-generated ROS. The ALA-induced mitochondrial damage might be a key event in the liver mitochondrial damage of acute intermittent porphyria patients reported elsewhere.
