FIGURE 2: The arsenal of mitochondrial antioxidant defenses comprises the thioredoxin and peroxiredoxin pathways. The image depicts redox reactions catalyzed by the thioredoxin and peroxiredoxin systems, comprising thioredoxin reductases (TrxR, of which ThxR2 is expressed in mitochondria), thioredoxins (Trx), peroxiredoxins (Prx) and NADPH. The electron source is NADPH, which mostly originates from the pentose phosphate pathway (PPP). Oxidized thioredoxins (Trx-S2) are reduced by NADPH and selenoenzymes TrxRs. Electrons are sequentially transferred from NADPH to FAD, to the N-terminal redox active disulfide in one subunit of TrxR, and, finally, to the C-terminal active site of another subunit. Reduced thioredoxins (Trx-SH₂) catalyze disulfide bond reduction in many proteins, including Prxs, thus ensuring oxidative damage repair in proteins as well as H₂O₂ detoxification.