Identification of an ATP-sensitive potassium channel in mitochondria

Mitochondria provide chemical energy for endoergonic reactions in form of ATP. Their activity must meet cellular energy requirements, but mechanisms linking organelle performance to ATP levels are poorly understood. Here, we identify a mitochondria-localized protein complex that mediates ATP-dependent potassium currents, referred to as mitoK(ATP). We show that similarly to their plasma membrane counterparts, mitoK(ATP) channels are composed of pore-forming (MITOK) and ATP-binding (MITOSUR) subunits. In vitro reconstitution of MITOK together with MITOSUR recapitulates the main properties of mitoK(ATP). While MITOK overexpression triggers dramatic organelle swelling, its genetic ablation causes instability of mitochondrial membrane potential, widening of intracristal space and decreased oxidative phosphorylation. Most importantly, loss of Mitok suppresses cardioprotection elicited by diazoxide-induced pharmacological preconditioning. Our data indicate that mitoK(ATP) channels respond to the cellular energetic status by regulating organelle volume and function, thereby representing key players in mitochondrial physiology with potential impact on several pathological processes.