Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: EC:3.1.4.1 (
phosphodiesterase
)
18,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We have previously demonstrated in H295R adrenocortical cells that the Ca
2+
-dependent production of mitochondrial cAMP (mt-cAMP) by the matrix soluble adenylyl cyclase (sAC; encoded by
ADCY10
) is associated with enhanced aldosterone production. Here, we examined whether mitochondrial sAC and mt-cAMP fine tune mitochondrial Ca
2+
metabolism to support steroidogenesis. Reduction of mt-cAMP formation resulted in decelerated mitochondrial Ca
2+
accumulation in intact cells during K
+
-induced Ca
2+
signalling and also in permeabilized cells exposed to elevated perimitochondrial [Ca
2+
]. By contrast, treatment with the membrane-permeable cAMP analogue 8-Br-cAMP, inhibition of
phosphodiesterase
2 and overexpression of sAC in the mitochondrial matrix all intensified Ca
2+
uptake into the organelle. Identical mt-cAMP dependence of mitochondrial Ca
2+
uptake was also observed in HeLa cells. Importantly, the enhancing effect of mt-cAMP on Ca
2+
uptake was independent from both the mitochondrial membrane potential and Ca
2+
efflux, but was reduced by Epac1 (also known as
RAPGEF3
) blockade both in intact and in permeabilized cells. Finally, overexpression of sAC in the mitochondrial matrix potentiated aldosterone production implying that the observed positive feedback mechanism of mt-cAMP on mitochondrial Ca
2+
accumulation may have a role in the rapid initiation of steroidogenesis.This article has an associated First Person interview with the first author of the paper.
...
PMID:Mitochondrial cAMP exerts positive feedback on mitochondrial Ca
2+
uptake via the recruitment of Epac1. 2966 48
