title: The role of mitochondrial Ca(2+) and NAD(P)H in the control of aldosterone secretion.
abstract: The mineralocorticoid hormone aldosterone is synthesized in the zona glomerulosa of the adrenal cortex. Glomerulosa cells respond to the physiological stimuli, elevated extracellular [K(+)] and angiotensin II, with an intracellular Ca(2+) signal. Cytosolic Ca(2+) facilitates the transport of the steroid-precursor cholesterol to mitochondria and, after a few hours, it also induces the transcription of aldosterone synthase. Therefore, the cytosolic Ca(2+) signal is regarded as the most important short and long-term mediator of aldosterone secretion. However, cytosolic Ca(2+) is also taken up by mitochondria and, in turn, the mitochondrial Ca(2+) response activates mitochondrial dehydrogenases resulting in stimulation of respiration and increase in reduced pyridine nucleotides. Since both cholesterol side-chain cleavage and all of the hydroxylation steps of steroid synthesis require NADPH as a cofactor, the importance of cytosolic Ca(2+) - mitochondrial Ca(2+) coupling and of appropriate NADPH supply in respect to hormone production can be assumed. However, the importance of the mitochondrial factors has been neglected so far. Here, after summarizing earlier findings we provide new results obtained through modifying mitochondrial Ca(2+) uptake by knocking down p38 MAPK or OPA1 and overexpressing S100G, supporting the notion that mitochondrial Ca(2+) and reduced pyridine nucleotides are facilitating factors for both basal and stimulated steroid production.
authors.affiliation: Department of Physiology, Faculty of Medicine, Semmelweis University, Hungary. spat.andras@eok.sote.hu
authors.forename: András
authors.initials: A
authors.lastname: Spät
authors.forename: László
authors.initials: L
authors.lastname: Fülöp
authors.forename: Gergő
authors.initials: G
authors.lastname: Szanda
mesh_terms: D000450:Aldosterone / Q000096:biosynthesis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000804:Angiotensin II; D000450:Aldosterone; D009249:NADP; D048051:p38 Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D011188:Potassium; D002118:Calcium