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Feedback Control of Adrenal Steroidogenesis via H2O2-Dependent, Reversible Inactivation of Peroxiredoxin III in Mitochondria

Title
Feedback Control of Adrenal Steroidogenesis via H2O2-Dependent, Reversible Inactivation of Peroxiredoxin III in Mitochondria
Authors
Kil I.S.Lee S.K.Ryu K.W.Woo H.A.Hu M.-C.Bae S.H.Rhee S.G.
Ewha Authors
이서구배수한길인섭우현애
SCOPUS Author ID
이서구scopusscopus; 우현애scopus
Issue Date
2012
Journal Title
Molecular Cell
ISSN
1097-2765JCR Link
Citation
vol. 46, no. 5, pp. 584 - 594
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Certain members of the peroxiredoxin (Prx) family undergo inactivation through hyperoxidation of the catalytic cysteine to sulfinic acid during catalysis and are reactivated by sulfiredoxin; however, the physiological significance of this reversible regulatory process is unclear. We now show that PrxIII in mouse adrenal cortex is inactivated by H2O2 produced by cytochrome P450 enzymes during corticosterone production stimulated by adrenocorticotropic hormone. Inactivation of PrxIII triggers a sequence of events including accumulation of H2O2, activation of p38 mitogen-activated protein kinase, suppression of steroidogenic acute regulatory protein synthesis, and inhibition of steroidogenesis. Interestingly, levels of inactivated PrxIII, activated p38, and sulfiredoxin display circadian oscillations. Steroidogenic tissue-specific ablation of sulfiredoxin in mice resulted in the persistent accumulation of inactive PrxIII and suppression of the adrenal circadian rhythm of corticosterone production. The coupling of CYP11B1 activity to PrxIII inactivation provides a feedback regulatory mechanism for steroidogenesis that functions independently of the hypothalamic-pituitary-adrenal axis. © 2012 Elsevier Inc.
DOI
10.1016/j.molcel.2012.05.030
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일반대학원 > 생명·약학부 > Journal papers
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