Figure 4.

Antioxidant defense mechanism in mitochondria. Mitochondria is the primary site for generation of ATP, which is the energy needed for cellular machinery. In addition to energy, ROS are produced, which results in cellular damage. The most commonly known ROS are hydrogen peroxide (H₂O₂₎, superoxide (O₂^–), and hydroxyl ions (OH^–). Superoxide generated in mitochondria is converted to H₂O₂ by the enzyme Mn-SOD. The H₂O₂ is further degraded to water by 2 defense mechanisms: (i) Glutathione peroxidase (GPx) catalyzes the reaction, whereby GSH reacts with H₂O₂ and converts it to glutathione disulfide (GSSG) and water (H₂O). Glutathione reductase (GSR) then reduces the oxidized glutathione (GSSG) to GSH. (ii) As a second mode of defense the H₂O₂ is converted into H₂O and molecular oxygen (O₂) by the mitochondrial catalase. Any superoxide that escapes mitochondria is again attacked by the SOD (Cu/Zn) present in the cytosol, which is again converted to H₂O₂ and this peroxide is decomposed by GPx and Catalase present in the cytoplasm and peroxisomes, respectively. The last destination for an electron along this chain is an oxygen molecule. Normally the oxygen is reduced to produce water; however, few of the electrons passing through the chain leak resulting in the generation of O₂^–. The most common site for electron leak are complexes I and III. Superoxide is not particularly reactive by itself, but can inactivate specific enzymes or initiate the formation of OH^– (depicted in red in dotted lines). Accumulation of OH^– in mitochondria could lead to release of cyt C from mitochondria leading to apoptosis. The diagram also depicts the TCA cycle which takes place in the matrix of the mitochondria. To be noted: the diagram depicts NADH being generated by malate dehydrogenase, but in TCA cycle NADH is also generated by isocitrate dehydrogenase and α-ketoglutarate dehydrogenase.