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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Commentary

An NADPH sensor that regulates cell ferroptosis

Authors: Guixing Kuang, Weidong Wang, Dan Xiong, Chong Zeng

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Ferroptosis is a new form of programmed cell death, which achieved great breakthroughs in cell biology during past decade. However, the regulation of ferroptosis is yet to be identified thoroughly. The latest study published on Nature cell biology by Nguyen and colleagues found a new NADPH sensor, MARCHF6 an E3 ubiquitin ligase, mediates ferroptosis in tumor growth and animal development. This finding provides a novel insight into ubiquitin system and energy metabolism in regulation of ferroptosis, which may open up new avenues for tumor treatment.
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Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72.CrossRef
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Zhao L, Zhou X, Xie F, Zhang L, Yan H, Huang J, Zhang C, Zhou F, Chen J, Zhang L. Ferroptosis in cancer and cancer immunotherapy. Cancer Commun (Lond). 2022;42(2):88–116.CrossRef
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Ding CC, Rose J, Sun T, Wu J, Chen PH, Lin CC, Yang WH, Chen KY, Lee H, Xu E, et al. MESH1 is a cytosolic NADPH phosphatase that regulates ferroptosis. Nat Metab. 2020;2(3):270–7.CrossRef
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Nguyen KT, Mun SH, Yang J, Lee J, Seok OH, Kim E, Kim D, An SY, Seo DY, Suh JY, et al. The MARCHF6 E3 ubiquitin ligase acts as an NADPH sensor for the regulation of ferroptosis. Nat Cell Biol. 2022;24(8):1239–51.CrossRef
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Liu Y, Xu S, Huang Y, Liu S, Xu Z, Wei M, Liu J. MARCH6 promotes Papillary Thyroid Cancer development by destabilizing DHX9. Int J Biol Sci. 2021;17(13):3401–12.CrossRef
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Tan JME, van der Stoel MM, van den Berg M, van Loon NM, Moeton M, Scholl E, van der Wel NN, Kovacevic I, Hordijk PL, Loregger A, et al. The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting. Cell Rep. 2020;32(5):107944.CrossRef
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Zhang HL, Hu BX, Li ZL, Du T, Shan JL, Ye ZP, Peng XD, Li X, Huang Y, Zhu XY, et al. PKCbetaII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis. Nat Cell Biol. 2022;24(1):88–98.CrossRef
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Scott NA, Sharpe LJ, Brown AJ. The E3 ubiquitin ligase MARCHF6 as a metabolic integrator in cholesterol synthesis and beyond. Biochim Biophys Acta Mol Cell Biol Lipids. 2021;1866(1):158837.CrossRef
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Zeng C, Lin J, Zhang K, Ou H, Ke S, Liu Q, Wei Z, Dong X, Zeng X, Zeng L, et al: SHARPIN promotes cell proliferation of cholangiocarcinoma and inhibits ferroptosis via p53/SLC7A11/GPX4 signaling. Cancer Sci 2022.doi: 10.1111/cas.15531.
Metadata
Title
An NADPH sensor that regulates cell ferroptosis
Authors
Guixing Kuang
Weidong Wang
Dan Xiong
Chong Zeng
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03658-3

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