Control mechanisms of mitochondrial Ca 2+ uptake - feed-forward modulation of aldosterone secretion

G. Szanda, Anikó Rajki, A. Spät

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mitochondrial Ca 2+ signal activates metabolism by boosting pyridine nucleotide reduction and ATP synthesis or, if Ca 2+ sequestration is supraphysiological, may even lead to apoptosis. Although the molecular background of mitochondrial Ca 2+ uptake has recently been elucidated, the regulation of Ca 2+ handling is still not properly clarified. In human adrenocortical H295R cells we found a regulatory mechanism involving p38 MAPK and novel-type PKC isoforms. Upon stimulation with angiotensin II (AII) these kinases are activated typically prior to the release of Ca 2+ and - most probably by reducing the Ca 2+ permeation through the outer mitochondrial membrane - attenuate mitochondrial Ca 2+ uptake in a feed-forward manner. The biologic significance of the kinase-mediated reduction of mitochondrial Ca 2+ signal is also reflected by the attenuation of AII-mediated aldosterone secretion. As another feed-forward mechanism, we found in HEK-293T and H295R cells that Ca 2+ signal evoked either by IP 3 or by voltage-gated influx is accompanied by a concomitant cytosolic Mg 2+ signal. In permeabilized HEK-293T cells Mg 2+ was found to be a potent inhibitor of mitochondrial Ca 2+ uptake in the physiologic [Mg 2+] and [Ca 2+] range. Thus, these inhibitory mechanisms may serve not only as protection against mitochondrial Ca 2+ overload and subsequent apoptosis but also have the potential to substantially alter physiological responses.

Original languageEnglish
Pages (from-to)101-108
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume353
Issue number1-2
DOIs
Publication statusPublished - Apr 28 2012

Fingerprint

HEK293 Cells
Aldosterone
Angiotensin II
Phosphotransferases
Modulation
Apoptosis
Mitochondrial Membranes
p38 Mitogen-Activated Protein Kinases
Metabolism
Permeation
Protein Isoforms
Nucleotides
Adenosine Triphosphate
Membranes
Electric potential
pyridine

Keywords

  • Aldosterone
  • Ca signaling
  • H295R
  • Mg
  • Mitochondria
  • P38 MAPK

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Biochemistry

Cite this

Control mechanisms of mitochondrial Ca 2+ uptake - feed-forward modulation of aldosterone secretion. / Szanda, G.; Rajki, Anikó; Spät, A.

In: Molecular and Cellular Endocrinology, Vol. 353, No. 1-2, 28.04.2012, p. 101-108.

Research output: Contribution to journalArticle

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