Role of soluble adenylyl cyclase in cell death and growth.

cAMP signaling is an evolutionarily conserved intracellular communication system controlling numerous cellular functions. Until recently, transmembrane adenylyl cyclase (tmAC) was considered the major source for cAMP in the cell, and the role of cAMP signaling was therefore attributed exclusively to the activity of this family of enzymes. However, increasing evidence demonstrates the role of an alternative, intracellular source of cAMP produced by type 10 soluble adenylyl cyclase (sAC). In contrast to tmAC, sAC produces cAMP in various intracellular microdomains close to specific cAMP targets, e.g., in nucleus and mitochondria. Ongoing research demonstrates involvement of sAC in diverse physiological and pathological processes. The present review is focused on the role of cAMP signaling, particularly that of sAC, in cell death and growth. Although the contributions of sAC to the regulation of these cellular functions have only recently been discovered, current data suggest that sAC plays key roles in mitochondrial bioenergetics and the mitochondrial apoptosis pathway, as well as cell proliferation and development. Furthermore, recent reports suggest the importance of sAC in several pathologies associated with apoptosis as well as in oncogenesis. This article is part of a Special Issue entitled: The role of soluble adenylyl cyclase in health and disease.