MTP 131 is a mitochondria-targeted peptide antioxidant.1,2It localizes to the mitochondria and reducestert-butyl hydroperoxide-induced lipid peroxidation and apoptosis in SH-SY5Y cells when used at concentrations ranging from 0.001 to 1 nM.1MTP 131 (2 mg/kg) reduces infarct volume, hemispheric swelling, and glutathione (GSH) depletion in a mouse model of acute cerebral ischemia induced by middle cerebral artery occlusion (MCAO).2It increases survival, improves motor function, and decreases degeneration of the lumbar spinal cord in a superoxide dismutase 1 mutant (SOD1G93A) transgenic mouse model of amyotrophic lateral sclerosis (ALS) when administered at a dose of 5 mg/kg. MTP 131 reduces albuminuria, urinary hydrogen peroxide levels, and mesangial matrix accumulation, as well as preserves superoxide production, in adb/dbmouse model of diabetic nephropathy.3
1.Zhao, K., Luo, G., Giannelli, S., et al.Mitochondria-targeted peptide prevents mitochondrial depolarization and apoptosis induced by tert-butyl hydroperoxide in neuronal cell linesBiochem. Pharmacol.70(12)1796-1806(2005) 2.Szeto, H.H.Mitochondria-targeted peptide antioxidants: Novel neuroprotective agentsAAPS J.8(3)E521-E531(2006) 3.Miyamoto, S., Zhang, G., Hall, D., et al.Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protects db/db mice against progression of diabetic kidney diseaseJ. Biol. Chem.295(21)7249-7260(2020)

Pretreatment of cells with MTP 131 (acetate) inhibited H2O2?induced cytotoxicity and reduced LDH release in a dose?dependent manner, compared with cells treated with H2O2 alone. Mitochondrial depolarization and ROS generation were also prevented by MTP 131 (acetate) pretreatment. In addition, MTP 131 (acetate) pretreatment inhibited cytochrome c release from mitochondria to cytoplasm, and significantly reduced apoptosis in RGC?5 cells, compared with cells treated with H2O2 alone[1].

18-week-old db/db mice have reduced renal and cardiac superoxide levels, as measured by dihydroethidium oxidation, and increased levels of albuminuria, mesangial matrix accumulation, and urinary H2O2 Administration of MTP 131 (acetate) significantly inhibited increases in albuminuria, urinary H2O2, and mesangial matrix accumulation in db/db mice and fully preserved levels of renal superoxide production in these mice. MTP 131 (acetate) also reduced total renal lysocardiolipin and major lysocardiolipin subspecies and preserved lysocardiolipin acyltransferase 1 expression in db/db mice[1].