Fig. 8. Role of cardiolipin (CL) in spinal cord injury (SCI).

Schematic drawing shows that SCI-induced CL alterations (peroxidation and loss) and downstream cascades leading to apoptotic cell death and functional impairment. Under normal circumstances, cardiolipin binds and retains cytochrome c (cyt c) in its native molten-globule structure at the inner mitochondrial membrane, keeping it close to the electron transport chain. (Left) During SCI, however, a massive production of ROS leads to accumulation of unfolding of cyt c, enhancing cyt c’s peroxidase activity, which targets polyunsaturated acyl chains of CL and induces CL peroxidation. ROS also induces cPLA₂ activation, which hydrolyzes CL and induces CL loss. Oxidation and loss of CL weakens and decreases its interaction with cyt c, which is now released and escapes to the cytosol via permeabilization of the outer mitochondrial membrane, triggering apoptosis and functional impairment. (Right) Treating SCI with XJB-5-131 (XJB), a novel mitochondria-targeted antioxidant, blocks CL alteration, attenuates apoptotic cell death, and improves functional recovery.