Journal Article

DKFZ-2024-02325

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Chen, Z. ; Inague, A. ; Kaushal, K.DKFZ* ; Fazeli, G. ; Schilling, D.DKFZ* ; Xavier da Silva, T. N. ; Dos Santos, A. F. ; Cheytan, T.DKFZ* ; Freitas, F. P. ; Yildiz, U. ; Viviani, L. G. ; Lima, R. S. ; Pinz, M. P. ; Medeiros, I. ; Iijima, T. S. ; Alegria, T. G. P. ; Pereira da Silva, R. ; Diniz, L. R. ; Weinzweig, S. ; Klein-Seetharaman, J. ; Trumpp, A.DKFZ* ; Mañas, A. ; Hondal, R. ; Bartenhagen, C. ; Fischer, M. ; Shimada, B. K. ; Seale, L. A. ; Chillon, T. S. ; Fabiano, M. ; Schomburg, L. ; Schweizer, U. ; Netto, L. E. ; Meotti, F. C. ; Dick, T. P.DKFZ* ; Alborzinia, H.DKFZ* ; Miyamoto, S. ; Friedmann Angeli, J. P.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.molcel.2024.10.027

Abstract: Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (H2SePO3-), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY. Mechanistically, we demonstrate that PRDX6 can readily react with selenide and interact with SEPHS2, potentially acting as a selenium delivery system. Moreover, we demonstrate the functional significance of this alternative route in human cancer cells, revealing a notable association between elevated expression of PRDX6 and human MYCN-amplified neuroblastoma subtype. Our study sheds light on a previously unrecognized aspect of Sec metabolism and its implications in ferroptosis, offering further possibilities for therapeutic exploitation.

Keyword(s): cancer metabolism ; cell death ; ferroptosis ; neuroblastoma ; selenium ; selenocysteine metabolism

Note: DKFZ-ZMBH Alliance / 84(23), pp. 4645–4659.e9

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Contributing Institute(s):

1. A010 Stammzellen und Krebs (A010)
2. A160 Redoxregulation (A160)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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