Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 8, pp 1141–1148 | Cite as

Mitochondrial cAMP and Ca2+ metabolism in adrenocortical cells

  • András SpätEmail author
  • Gergő Szanda
Invited Review


The biological effects of physiological stimuli of adrenocortical glomerulosa cells are predominantly mediated by the Ca2+ and the cAMP signal transduction pathways. The complex interplay between these signalling systems fine-tunes aldosterone secretion. In addition to the well-known cytosolic interactions, a novel intramitochondrial Ca2+–cAMP interplay has been recently recognised. The cytosolic Ca2+ signal is rapidly transferred into the mitochondrial matrix where it activates Ca2+-sensitive dehydrogenases, thus enhancing the formation of NADPH, a cofactor of steroid synthesis. Quite a few cell types, including H295R adrenocortical cells, express the soluble adenylyl cyclase within the mitochondria and the elevation of mitochondrial [Ca2+] activates the enzyme, thus resulting in the Ca2+-dependent formation of cAMP within the mitochondrial matrix. On the other hand, mitochondrial cAMP (mt-cAMP) potentiates the transfer of cytosolic Ca2+ into the mitochondrial matrix. This cAMP-mediated positive feedback control of mitochondrial Ca2+ uptake may facilitate the rapid hormonal response to emergency situations since knockdown of soluble adenylyl cyclase attenuates aldosterone production whereas overexpression of the enzyme facilitates steroidogenesis in vitro. Moreover, the mitochondrial Ca2+–mt-cAMP–Ca2+ uptake feedback loop is not a unique feature of adrenocortical cells; a similar signalling system has been described in HeLa cells as well.


cAMP Ca2+ signal Mitochondria Aldosterone Soluble adenylyl cyclase Adrenocortical cells 



We thank Dr. G. Di Benedetto, Dr. D. Katona, Prof. T. Pozzan, Ms. A. Rajki and Dr. É. Wisniewski for their contribution to the experimental work presented in this review. The discussions with Professors Erzsébet Ligeti and László Tretter and Miklós Geiszt are also appreciated.

Funding information

The study received financial support from the Hungarian National Science Foundation (OTKA NK100883, 108382 and K116954), the János Bólyai Research Scholarship of the Hungarian Academy of Sciences to G.S. and the National Research, Development and Innovation Office (NKFI-6/FK_124038 to G.S.).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PhysiologySemmelweis University Medical SchoolBudapestHungary
  2. 2.MTA-SE Laboratory of Molecular Physiology, Semmelweis UniversityHungarian Academy of SciencesBudapestHungary

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