The action of irradiated cationic Fe(III)TMPyP and anionic Fe(III)TPPS4 forms of mesoporphyrins on mitochondrial functions was investigated using experimental condition that caused minimal effects on mitochondria in the dark. Treatment of mitochondria with 1 mu M Fe(III)TMPyP for 2 min decreased the respiratory control by 3% in the dark and 28% after irradiation. Fe(III)TPPS4 (1 mu M) had no significant effect oil respiratory control under any of the above conditions. Both porphyrins increased the mitochondrial production of reactive oxygen species in the presence of Ca2+; however, the effect of Fe(III)TMPyP was significantly stronger. In both cases, this overproduction was associated with membrane lipid peroxidation. It was also observed that the association constant of Fe(III)TMPyP with mitochondria was I I times higher than that of Fe(III)TPPS4. In Conclusion, the damage to isolated mitochondria induced by Fe(III)TMPyP under illumination was larger than by Fe(III)TPPS4. probably because its cationic charge favors association with the mitochondrial membrane. This is supported by the decrease in the association constant of Fe(III)TMPyP with mitochondria in higher salt medium. (c) 2006 Elsevier Inc. All rights reserved.4572217224