Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury

Hazel H. Szeto, Shaoyi Liu, Yi Soong, Dunli Wu, Shaun F. Darrah, Feng Ying Cheng, Zhihong Zhao, Michael Ganger, Clara Y. Tow, Surya V. Seshan

Research output: Contribution to journalArticlepeer-review

238 Scopus citations


The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.

Original languageEnglish (US)
Pages (from-to)1041-1052
Number of pages12
JournalJournal of the American Society of Nephrology
Issue number6
StatePublished - Jun 2011
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury'. Together they form a unique fingerprint.

Cite this