Irisin: A Promising Target for Ischemia-Reperfusion Injury Therapy

Figure 3

The mechanistic correlation between irisin and IRI. Exercise induces the expression of transcriptional coactivator PGC1-α and its downstream gene FNDC5, after which FNDC5 is cleaved and secreted into the circulation. An effective splice product of FNDC5 is named irisin. (1) Imbalance of the oxidant-antioxidant system triggers oxidative stress during IRI. Irisin exerts protective effects on IRI by activating the antioxidant components and inhibiting the expression and activity of oxidases. (2) ETC-related mitochondrial oxidative stress, abnormal mitochondrial permeability, and unbalanced mitochondrial dynamics all mediate mitochondrial dysfunction and IRI deterioration, while irisin exerts mitochondrial protection to reverse above changes. (3) The activation of the initial inflammatory response and the subsequent amplification of the inflammatory cascades during IRI can be improved by irisin. ETC: electron transport chain. FNDC5: fibronectin type III domain-containing protein 5; IRI: ischemia-reperfusion injury; PGC1-α: PPAR-c coactivator-1 α.