DJ-1 suppresses ferroptosis through preserving the activity of S-adenosyl homocysteine hydrolase.

Nature Communications
Ji CaoMeidan Ying

Abstract

Ferroptosis is a newly characterized form of regulated cell death mediated by iron-dependent accumulation of lipid reactive oxygen species and holds great potential for cancer therapy. However, the molecular mechanisms underlying ferroptosis remain largely elusive. In this study, we define an integrative role of DJ-1 in ferroptosis. Inhibition of DJ-1 potently enhances the sensitivity of tumor cells to ferroptosis inducers both in vitro and in vivo. Metabolic analysis and metabolite rescue assay reveal that DJ-1 depletion inhibits the transsulfuration pathway by disrupting the formation of the S-adenosyl homocysteine hydrolase tetramer and impairing its activity. Consequently, more ferroptosis is induced when homocysteine generation is decreased, which might be the only source of glutathione biosynthesis when cystine uptake is blocked. Thus, our findings show that DJ-1 determines the response of cancer cells to ferroptosis, and highlight a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.

References

Nov 24, 1999·Free Radical Biology & Medicine·O W Griffith
Dec 4, 2003·Biochemical and Biophysical Research Communications·Takanori YokotaHidehiro Mizusawa
Jan 30, 2004·EMBO Reports·Takahiro TairaHiroyoshi Ariga
Feb 28, 2004·The Journal of Nutrition·Guoyao WuNancy D Turner
Jul 20, 2004·Journal of Cellular Biochemistry·Yaacov Hod
Aug 17, 2005·Cancer Research·Ying HuangWolfgang Sadée
Oct 18, 2005·The Journal of Biological Chemistry·Wenbo Zhou, Curt R Freed
Oct 4, 2006·Proceedings of the National Academy of Sciences of the United States of America·Casey M ClementsJenny P-Y Ting
Jun 7, 2008·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Benoit DevogelaereHumbert De Smedt
Aug 30, 2008·Biochemical and Biophysical Research Communications·Hang LiuJianxiang Wang
Sep 4, 2010·Antioxidants & Redox Signaling·Mark A Wilson
Jul 13, 2011·International Journal of Molecular Sciences·Hua-Zong ZengAi-Bin Liang
Feb 3, 2012·Bioorganic & Medicinal Chemistry Letters·Michel WeïwerBenito Munoz
Apr 24, 2012·Human Molecular Genetics·Ju-young LeeChankyu Park
Apr 25, 2012·Journal of Cancer Research and Clinical Oncology·Ying ChenYulian Wu
May 29, 2012·Cell·Scott J DixonBrent R Stockwell
Jun 13, 2012·Biological & Pharmaceutical Bulletin·Ismail Ahmed IsmailSu-Hyung Hong
Nov 28, 2012·Biochemical and Biophysical Research Communications·Rosa Milagros CorralesLaurent Kremer
Dec 4, 2012·Biochimica Et Biophysica Acta·Regina Brigelius-Flohé, Matilde Maiorino
Jan 21, 2014·Cell·Wan Seok YangBrent R Stockwell
Mar 7, 2014·Journal of the American Chemical Society·Rachid SkoutaBrent R Stockwell
Sep 25, 2014·The Journal of Biological Chemistry·Yun WangPhilip A Cole
Dec 17, 2014·Biochemical Pharmacology·Ji CaoBo Yang
Sep 26, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaofang SunDaolin Tang
Dec 15, 2015·Trends in Cell Biology·Wan Seok Yang, Brent R Stockwell
May 10, 2016·Nature Chemical Biology·Kenichi ShimadaBrent R Stockwell
Nov 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yang OuWei Gu
Nov 15, 2016·Nature Chemical Biology·Sebastian DollMarcus Conrad
Jun 10, 2017·Science·Gilbert RicharmeAazdine Lamouri
Jan 19, 2018·Cell Reports·Amy TarangeloScott J Dixon
Jan 30, 2018·Frontiers in Pharmacology·Bin LuBo Yang
Feb 24, 2018·Clinica Chimica Acta; International Journal of Clinical Chemistry·G Nagesh BabuRaja Roy
Oct 22, 2019·Nature·Sebastian DollMarcus Conrad
Oct 22, 2019·Nature·Kirill BersukerJames A Olzmann

❮ Previous
Next ❯

Citations

Aug 18, 2020·Autophagy·Xin ChenDaolin Tang
Sep 4, 2020·Experimental Biology and Medicine·Santosh R D'Mello, Mark C Kindy
Sep 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ana HipólitoJacinta Serpa
Oct 18, 2020·Biomedicines·Maria EjmaGjumrakch Aliev
Jan 28, 2021·Biology·Min Ji KimSung Eun Kim
Feb 5, 2021·Signal Transduction and Targeted Therapy·Hong-Fa YanPeng Lei
Nov 24, 2020·British Journal of Cancer·Vasco D B BonifácioJoão B Vicente
Jan 12, 2021·Oxidative Medicine and Cellular Longevity·Jinghan ZhuWanguang Zhang
Feb 5, 2021·Ageing Research Reviews·P A DionísioC M P Rodrigues
Nov 14, 2020·Movement Disorders : Official Journal of the Movement Disorder Society·David DevosRichard Wyse
Jul 30, 2020·Progress in Neurobiology·Laura Mahoney-SánchezJean-Christophe Devedjian
Apr 2, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Haiyan WangYongguang Tao
Mar 28, 2021·The FEBS Journal·Carson D Poltorack, Scott J Dixon
Nov 21, 2020·Cell Metabolism·Jiashuo Zheng, Marcus Conrad
May 28, 2021·Veterinary Pathology·Sara Francesca SantagostinoEnrico Radaelli
Aug 20, 2020·Neuro-degenerative Diseases·Juepu ZhouHonglei Wang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transmission electron microscopy
enzyme-linked immunosorbent assay
ELISA
immunoprecipitation
acetylation
size-exclusion chromatography
transfection
xenograft
dissection

Software Mentioned

Leica Application Suite
GraphPad
Leica
QuantStudio
FlowJo
Xcalibur
SoftMax Pro
Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.