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

Authors
 In Sup Kil  ;  Se Kyoung Lee  ;  Keun Woo Ryu  ;  Hyun Ae Woo  ;  Meng-Chun Hu  ;  Soo Han Bae  ;  Sue Goo Rhee 
Citation
 Molecular Cell, Vol.46(5) : 584-594, 2012 
Journal Title
 Molecular Cell 
ISSN
 1097-2765 
Issue Date
2012
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91474
DOI
10.1016/j.molcel.2012.05.030
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부)
Yonsei Authors
길인섭(Kil, In Sup)
배수한(Bae, Soo Han)
이서구(Rhee, Sue Goo)
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