ROLE of MITOCHONDRIA in TOXIC OXIDATIVE STRESS

Proposed scheme of events in MPTP-induced mitochondrial O₂·⁻toxicity via oxidative aconitase inactivation. The fate of mitochondrial O₂·⁻ is normally controlled by its reactivity with several targets that include Sod2, nitric oxide NO, and Fe-S centers. Elevated steady-state mitochondrial O₂·⁻ production resulting from Complex I inhibition by MPTP’s active metabolite, MPP⁺, would favor oxidative inactivation of the [4Fe-4S]²⁺-containing aconitase and simultaneous release of Fe²⁺ and H₂O₂. Subsequent generation of HO· via Fenton chemistry could damage mitochondrial proteins, DNA, and lipids thereby amplifying O₂ ⁻initiated oxidative damage. Additionally, the release of Fe may affect cellular iron homeostasis and decreased aconitase activity could interrupt its TCA cycle function. Adapted from (137).