Ischemic preconditioning (IPC) is an evolutionarily conserved endogenous mechanism whereby short periods of non-lethal exposure to hypoxia alleviate damage caused by subsequent ischemia reperfusion (IR). Pharmacologic targeting has suggested that the mitochondrial ATP-sensitive potassium channel (mK(ATP)) is central to IPC signaling, despite its lack of molecular identity. Here, we report that isolated Caenorhabditis elegans mitochondria have a K-ATP channel with the same physiologic and pharmacologic characteristics as the vertebrate channel. Since C. elegans also exhibit IPC, our observations provide a framework to study the role Of mK(ATP) in IR injury in a genetic model organism. (C) 2008 Elsevier Inc. All rights reserved.