cAMP-PKA signaling to the mitochondria: protein scaffolds, mRNA and phosphatases

Energy metabolism and, specifically, the coupling of mitochondria to growth and survival is controled by the cAMP-PKA pathway in yeast. In higher eukaryotes, cAMP signaling originating at the plasma membrane is distributed to different subcellullar districts by cAMP waves received by PKA bound to PKA anchor proteins (AKAPs) tethered to the-se compartments. This review focuses on the subgroup of AKAPs that anchor PKA to the mitochondrial outer membrane (mtAKAPs). Only PKA anchored to mtAKAPs can efficiently transmit CAN-W signals to mitochondria. mtAKAP complexes are remarkably heterogeneous. In addition to PKA regulatory subunits they may include mRNAs, tyrosine phosphatase(s) and tyrosine kinase(s). Selective regulation of these components by cAMP-PKA integrates various signal transduction pathways and can determine which subcellular compartment receives the signal. Unveiling the interactions among the components of these large complexes will shed light on how cAMP and PKA regulate vital monochondrial processes. (C) 2004 Elsevier Inc. All rights reserved.