title: Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion.
abstract: Glomerulosa cells secrete aldosterone in response to agonists coupled to Ca(2+) increases such as angiotensin II and corticotrophin, coupled to a cAMP dependent pathway. A recently recognized interaction between Ca(2+) and cAMP is the Ca(2+)-induced cAMP formation in the mitochondrial matrix. Here we describe that soluble adenylyl cyclase (sAC) is expressed in H295R adrenocortical cells. Mitochondrial cAMP formation, monitored with a mitochondria-targeted fluorescent sensor (4mtH30), is enhanced by HCO3(-) and the Ca(2+) mobilizing agonist angiotensin II. The effect of angiotensin II is inhibited by 2-OHE, an inhibitor of sAC, and by RNA interference of sAC, but enhanced by an inhibitor of phosphodiesterase PDE2A. Heterologous expression of the Ca(2+) binding protein S100G within the mitochondrial matrix attenuates angiotensin II-induced mitochondrial cAMP formation. Inhibition and knockdown of sAC significantly reduce angiotensin II-induced aldosterone production. These data provide the first evidence for a cell-specific functional role of mitochondrial cAMP.
authors.affiliation: Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: Dávid
authors.initials: D
authors.lastname: Katona
authors.affiliation: Laboratory of Molecular Physiology, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Rajki
authors.affiliation: Institute of Neuroscience, Italian National Research Council, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Giulietta
authors.initials: G
authors.lastname: Di Benedetto
authors.affiliation: Institute of Neuroscience, Italian National Research Council, Padova, Italy; Venetian Institute of Molecular Medicine, Padova, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Pozzan
authors.affiliation: Department of Physiology, Semmelweis University Medical School, Budapest, Hungary. Electronic address: spat@eok.sote.hu.
authors.forename: András
authors.initials: A
authors.lastname: Spät
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D000804:Angiotensin II / Q000502:physiology; D020013:Calcium Signaling; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D000242:Cyclic AMP; C579271:ADCY10 protein, human; D000262:Adenylyl Cyclases
keywords: Aldosterone; Angiotensin II; Ca2 + signal, glomerulosa cell; Cyclic AMP; Mitochondria; Soluble adenylyl cyclase