Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels

Transduction of energetic signals into membrane electrical events governs v ital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such dive rse cellular processes are the metabolism sensing ATP-sensitive K+ (K-ATP) channels. However, the mechanism that communicates metabolic signals and in tegrates cellular energetics with K-ATP channel-dependent membrane excitabi lity remains elusive. Here, we identify that the response of KATP channels to metabolic challenge is regulated by adenylate kinase phosphotransfer. Ad enylate kinase associates with the K-ATP channel complex, anchoring cellula r phosphotransfer networks and facilitating delivery of mitochondrial signa ls to the membrane environment. Deletion of the adenylate kinase gene compr omised nucleotide exchange at the channel site and impeded communication be tween mitochondria and KATP channels, rendering cellular metabolic sensing defective. Assigning a signal processing role to adenylate kinase identifie s a phosphorelay mechanism essential for efficient coupling of cellular ene rgetics with KATP channels and associated functions.