Calcium-dependent mitochondrial cAMP production enhances aldosterone secretion. (5th September 2015)

• Record Type: Journal Article
• Authors: Katona, Dávid; Rajki, Anikó; Di Benedetto, Giulietta; Pozzan, Tullio; Spät, András
• Is Part Of: Molecular and cellular endocrinology. Volume 412(2015)
• Page Start: 196
• Page End: 204
• Publication Date: 2015-09-05
• Subjects: COX-IV cytochrome c oxidase IV -- mt-cAMP mitochondrial cAMP -- 2-OHE 2-hydroxy-estradiol -- sAC soluble adenylyl cyclase; Cyclic AMP -- Soluble adenylyl cyclase -- Mitochondria -- Aldosterone -- Angiotensin II -- Ca2 + signal, glomerulosa cell; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2015.05.002
• Languages: English
• ISSNs: 0303-7207

Abstract

Highlights: HCO3 − activates mitochondrial adenylyl cyclase (sAC) in human adrenocortical cells. Angiotensin II causes a mitochondrial [cAMP] rise in a [Ca 2+ ]mito -dependent way. cAMP signal is reduced by siRNA for sAC, and enhanced by PDE2-inhibitor. Inhibition of sAC attenuates angiotensin II-induced aldosterone secretion. Graphical Abstract: 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.