Extramitochondrial OPA1 and adrenocortical function

Fülöp, László and Rajki, Anikó and Katona, Dávid and Szanda, Gergö and Spät, András (2013) Extramitochondrial OPA1 and adrenocortical function. Molecular and Cellular Endocrinology, 381 (1-2). pp. 70-79. ISSN 0303-7207

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Abstract

We have previously described that silencing of the mitochondrial protein OPA1 enhances mitochondrial 27 Ca2+ signaling and aldosterone production in H295R adrenocortical cells. Since extramitochondrial OPA1 28 (emOPA1) was reported to facilitate cAMP-induced lipolysis, we hypothesized that emOPA1, via the 29 enhanced hydrolysis of cholesterol esters, augments aldosterone production in H295R cells. A few 30 OPA1 immunopositive spots were detected in �40% of the cells. In cell fractionation studies OPA1/COX 31 IV (mitochondrial marker) ratio in the post-mitochondrial fractions was an order of magnitude higher 32 than that in the mitochondrial fraction. The ratio of long to short OPA1 isoforms was lower in post-mito- 33 chondrial than in mitochondrial fractions. Knockdown of OPA1 failed to reduce db-cAMP-induced phos- 34 phorylation of hormone-sensitive lipase (HSL), Ca2+ signaling and aldosterone secretion. In conclusion, 35 OPA1 could be detected in the post-mitochondrial fractions, nevertheless, OPA1 did not interfere with 36 the cAMP – PKA – HSL mediated activation of aldosterone secretion

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