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Song, W.* ; Xin, S. ; He, M.* ; Pfeiffer, S. ; Cao, A.* ; Li, H.* ; Schick, J. ; Jin, X.*

Evolutionary and functional analyses demonstrate conserved ferroptosis protection by Arabidopsis GPXs in mammalian cells.

FASEB J. 35:e21550 (2021)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Species have evolved unique mechanisms to combat the effects of oxidative stress inside cells. A particularly devastating consequence of an unhindered oxidation of membrane lipids in the presence of iron results in cell death, known as ferroptosis. Hallmarks of ferroptosis, including peroxidation of polyunsaturated fatty acids, are conserved among animals and plants, however, early divergence of an ancestral mammalian GPX4 (mGPX4) has complicated our understanding of mechanistic similarities between species. To this end, we performed a comprehensive phylogenetic analysis and identified that orthologous Arabidopsis GPXs (AtGPXs) are more highly related to mGPX4 than mGPX4 is to other mammalian GPXs. This high degree of conservation suggested that experimental substitution may be possible. We, therefore, ectopically expressed AtGPX1-8 in ferroptosis-sensitive mouse fibroblasts. This substitution experiment revealed highest protection against ferroptosis induction by AtGPX5, as well as moderate protection by AtGPX2, -7, and -8. Further analysis of these cells revealed substantial abatement of lipid peroxidation in response to pharmacological challenge. The results suggest that the presence of ancestral GPX4 resulted in later functional divergence and specialization of GPXs in plants. The results also challenge a strict requirement for selenocysteine activity and suggest thioredoxin as a potent parallel antioxidant system in both plants and mammals.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Evolution ; Reactive Oxygen Species ; Selenoprotein ; Subcellular Location ; Thioredoxin; Hydroperoxide Glutathione-peroxidase; Genome-wide Identification; Gene Family; Thioredoxin Peroxidase; Antioxidant Enzymes; Expression Analysis; Selenium; Stress; Death; Classification
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Zeitschrift FASEB Journal
Quellenangaben Band: 35, Heft: 6, Seiten: , Artikelnummer: e21550 Supplement: ,
Verlag Wiley
Verlagsort Bethesda, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Toxicology and Pharmacology (TOXI)
Förderungen International Scientific and Technological Cooperation Project by Shihezi University
Helmholtz Zentrum Muenchen GmbH (JAS)