Figure 2.

Mitochondrial ROS/RNS generation is believed to act as the main cause of aconitase oxidative damage. One of the main functions of the TCA cycle is the generation of electrons used by the mitochondrial ETC to produce ATP. The multi-subunit complexes of ETC are located in the inner mitochondrial membrane. The electrons provided by NADH and FADH₂ from the TCA cycle are transmitted to NADH ubiquinone reductase (complex I) or succinate dehydrogenase (complex II), and then to ubiquinol-cytochrome c reductase (complex III), and finally to oxygen through cytochrome c oxidase (complex IV). The functioning of mitochondria is indissolubly connected with ROS production; firstly, superoxide anion (•O₂−). Superoxide is converted to hydrogen peroxide (H₂O₂) by the enzyme superoxide dismutase (SOD) in mitochondria. H₂O₂ is then converted to water by catalase (CAT). Superoxide can damage iron–sulfur proteins such as aconitase, subsequently releasing ferrous iron. The presence of ferrous iron promotes the formation of a hydroxyl radical (HO•) from hydrogen peroxide. Superoxide is also capable of reacting with nitric oxide (NO.) to form peroxynitrite (ONOO−). •O₂−, HO•, and ONOO− can cause extensive oxidative damage to aconitase. Abbreviations: CS, citrate synthase; Aco2, aconitase 2; IDH, isocitrate dehydrogenase; αKGDH, α-ketoglutarate dehydrogenase; SCS, succinyl-CoA synthetase; SDH, succinate dehydrogenase; FH, fumarate hydratase; MDH, malate dehydrogenase.