The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin

Birk AV, Liu S, Soong Y, et al. · Journal of the American Society of Nephrology

Demonstrated that SS-31 binds cardiolipin with high affinity (KD 1.87 µM), inhibits the cytochrome c peroxidase activity that damages mitochondria during ischemia (EC50 0.8 µM in permeabilised mitochondria), protects cristae membranes, and accelerates ATP recovery on reperfusion; serum creatinine at 24 hours was 0.62 mg/dL against 1.72 on saline and 0.39 in sham — the core mechanism paper, in kidney, not joint tissue.

Population

Rats (six per group) with 30 minutes of bilateral renal ischaemia; isolated kidney mitochondria; cell and lipid systems

Intervention

SS-31 2 mg/kg subcutaneously 30 minutes before ischaemia and again at reperfusion; fluorescent-analog binding studies

Comparator

Untreated ischemic controls

Limitations

Renal ischemia model from the originating (Szeto) lab; establishes mechanism, not any joint effect. NIH-funded, with the SS peptides licensed to Stealth, in which the senior author and Cornell hold financial interests.