171
Views
0
CrossRef citations to date
0
Altmetric
Articles

Effects of hexavalent chromium on mitochondria and their implications in carcinogenesis

, &

References

  • DesMarais TL, Costa M. Mechanisms of chromium-induced toxicity. Curr Opin Toxicol. 2019;14:1–7. doi:10.1016/j.cotox.2019.05.003.
  • Braver ER, Infante P, Chu K. An analysis of lung cancer risk from exposure to hexavalent chromium. Teratog Carcinog Mutagen. 1985;5(5):365–378. doi:10.1002/tcm.1770050507.
  • Costa M, Klein CB. Toxicity and carcinogenicity of chromium compounds in humans. Crit Rev Toxicol. 2006;36(2):155–163. doi:10.1080/10408440500534032.
  • Gibb HJ, Lees PS, Pinsky PF, Rooney BC. Lung cancer among workers in chromium chemical production. Am J Ind Med. 2000;38(2):115–126. doi:10.1002/1097-0274(200008)38:2<115::AID-AJIM1>3.0.CO;2-Y.
  • Halasova E, Matakova T, Kavcova E, et al. Human lung cancer and hexavalent chromium exposure. Neuro Endocrinol Lett. 2009;30(Suppl 1):182–185.
  • Holmes AL, Wise SS, Wise JP.Sr. Carcinogenicity of hexavalent chromium. Indian J Med Res. 2008;128(4):353–372.
  • Park RM, Bena JF, Stayner LT, Smith RJ, Gibb HJ, Lees PS. Hexavalent chromium and lung cancer in the chromate industry: a quantitative risk assessment. Risk Anal. 2004;24(5):1099–1108. doi:10.1111/j.0272-4332.2004.00512.x.
  • Islam S, Kamila S, Chattopadhyay A. Toxic and carcinogenic effects of hexavalent chromium in mammalian cells in vivo and in vitro: a recent update. J Environ Sci Health C Toxicol Carcinog. 2022;40(3-4):282–315. doi:10.1080/26896583.2022.2158675.
  • Deng Y, Wang M, Tian T, et al. The Effect of Hexavalent Chromium on the Incidence and Mortality of Human Cancers: A Meta-Analysis Based on Published Epidemiological Cohort Studies. Front Oncol. 2019;9:24. doi:10.3389/fonc.2019.00024.
  • Sun H, Brocato J, Costa M. Oral Chromium Exposure and Toxicity. Curr Environ Health Rep. 2015;2(3):295–303. doi:10.1007/s40572-015-0054-z.
  • National Toxicology Program. Toxicology and carcinogenesis studies of sodium dichromate dihydrate (Cas No. 7789-12-0) in F344/N rats and B6C3F1 mice (drinking water studies). Natl Toxicol Program Tech Rep Ser. 2008;546:1–192.
  • Zhitkovich A. Chromium in drinking water: sources, metabolism, and cancer risks. Chem Res Toxicol. 2011;24(10):1617–1629. doi:10.1021/tx200251t.
  • European Commission. RASFF annual report 2015. 2016.
  • Salnikow K, Zhitkovich A. Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol. 2008;21(1):28–44. doi:10.1021/tx700198a.
  • Shi X, Chiu A, Chen CT, Halliwell B, Castranova V, Vallyathan V. Reduction of chromium(VI) and its relationship to carcinogenesis. J Toxicol Environ Health B Crit Rev. 1999;2(1):87–104. doi:10.1080/109374099281241.
  • Ding M, Shi X. Molecular mechanisms of Cr(VI)-induced carcinogenesis. Mol Cell Biochem. 2002;234-235(1-2):293–300.
  • Borthiry GR, Antholine WE, Kalyanaraman B, Myers JM, Myers CR. Reduction of hexavalent chromium by human cytochrome b5: generation of hydroxyl radical and superoxide. Free Radic Biol Med. 2007;42(6):738–755. discussion 5-7. doi:10.1016/j.freeradbiomed.2006.10.055.
  • Stearns DM, Kennedy LJ, Courtney KD, Giangrande PH, Phieffer LS, Wetterhahn KE. Reduction of chromium(VI) by ascorbate leads to chromium-DNA binding and DNA strand breaks in vitro. Biochemistry. 1995;34(3):910–919. doi:10.1021/bi00003a025.
  • Krawic C, Luczak MW, Zhitkovich A. Variation in Extracellular Detoxification Is a Link to Different Carcinogenicity among Chromates in Rodent and Human Lungs. Chem Res Toxicol. 2017;30(9):1720–1729. doi:10.1021/acs.chemrestox.7b00172.
  • Liu KJ, Shi X. In vivo reduction of chromium (VI) and its related free radical generation. Mol Cell Biochem. 2001;222(1-2):41–47.
  • Zhitkovich A. Importance of chromium-DNA adducts in mutagenicity and toxicity of chromium(VI). Chem Res Toxicol. 2005;18(1):3–11. doi:10.1021/tx049774+.
  • Macfie A, Hagan E, Zhitkovich A. Mechanism of DNA-protein cross-linking by chromium. Chem Res Toxicol. 2010;23(2):341–347. doi:10.1021/tx9003402.
  • Wise SS, Aboueissa AE, Martino J, Wise JP.Sr. Hexavalent Chromium-Induced Chromosome Instability Drives Permanent and Heritable Numerical and Structural Changes and a DNA Repair-Deficient Phenotype. Cancer Res. 2018;78(15):4203–4214. doi:10.1158/0008-5472.CAN-18-0531.
  • Hu L, Liu X, Chervona Y, et al. Chromium induces chromosomal instability, which is partly due to deregulation of BubR1 and Emi1, two APC/C inhibitors. Cell Cycle. 2011;10(14):2373–2379. doi:10.4161/cc.10.14.16310.
  • Chen QY, Murphy A, Sun H, Costa M. Molecular and epigenetic mechanisms of Cr(VI)-induced carcinogenesis. Toxicol Appl Pharmacol. 2019;377:114636. doi:10.1016/j.taap.2019.114636.
  • Li P, Zhang X, Murphy AJ, Costa M, Zhao X, Sun H. Downregulation of hedgehog-interacting protein (HHIP) contributes to hexavalent chromium-induced malignant transformation of human bronchial epithelial cells. Carcinogenesis. 2021;42(1):136–147. doi:10.1093/carcin/bgaa085.
  • Handy DE, Loscalzo J. Redox regulation of mitochondrial function. Antioxid Redox Signal. 2012;16(11):1323–1367. doi:10.1089/ars.2011.4123.
  • Mailloux RJ, Jin X, Willmore WG. Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol. 2014;2:123–139. doi:10.1016/j.redox.2013.12.011.
  • James AM, Murphy MP. How mitochondrial damage affects cell function. J Biomed Sci. 2002;9(6):475–487. doi:10.1007/BF02254975.
  • Russell OM, Gorman GS, Lightowlers RN, Turnbull DM. Mitochondrial Diseases: Hope for the Future. Cell. 2020;181(1):168–188. doi:10.1016/j.cell.2020.02.051.
  • Kim M, Mahmood M, Reznik E, Gammage PA. Mitochondrial DNA is a major source of driver mutations in cancer. Trends Cancer. 2022;8(12):1046–1059. doi:10.1016/j.trecan.2022.08.001.
  • Arita A, Costa M. Epigenetics in metal carcinogenesis: nickel, arsenic, chromium and cadmium. Metallomics: integrated Biometal Science. 2009;1(3):222–228. doi:10.1039/b903049b.
  • O’Brien TJ, Ceryak S, Patierno SR. Complexities of chromium carcinogenesis: role of cellular response, repair and recovery mechanisms. Mutat Res. 2003;533(1-2):3–36. doi:10.1016/j.mrfmmm.2003.09.006.
  • Nickens KP, Patierno SR, Ceryak S. Chromium genotoxicity: A double-edged sword. Chem Biol Interact. 2010;188(2):276–288. doi:10.1016/j.cbi.2010.04.018.
  • Chiu A, Shi XL, Lee WK, et al. Review of chromium (VI) apoptosis, cell-cycle-arrest, and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2010;28(3):188–230. doi:10.1080/10590501.2010.504980.
  • Popov LD. Mitochondrial biogenesis: An update. J Cellular Molecular Medi. 2020;24(9):4892–4899. doi:10.1111/jcmm.15194.
  • Zhang B, Pan C, Feng C, et al. Role of mitochondrial reactive oxygen species in homeostasis regulation. Redox Rep. 2022;27(1):45–52. doi:10.1080/13510002.2022.2046423.
  • Park J, Lee J, Choi C. Mitochondrial network determines intracellular ROS dynamics and sensitivity to oxidative stress through switching inter-mitochondrial messengers. PLoS One. 2011;6(8):e23211. doi:10.1371/journal.pone.0023211.
  • Tirichen H, Yaigoub H, Xu W, Wu C, Li R, Li Y. Mitochondrial Reactive Oxygen Species and Their Contribution in Chronic Kidney Disease Progression Through Oxidative Stress. Front Physiol. 2021;12:627837. doi:10.3389/fphys.2021.627837.
  • Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev. 2014;94(3):909–950. doi:10.1152/physrev.00026.2013.
  • Li X, Fang P, Mai J, Choi ET, Wang H, Yang XF. Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers. J Hematol Oncol. 2013;6(1):19. doi:10.1186/1756-8722-6-19.
  • Pizzino G, Irrera N, Cucinotta M, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763–8416713. doi:10.1155/2017/8416763.
  • Kowaltowski AJ, Vercesi AE. Mitochondrial damage induced by conditions of oxidative stress. Free Radic Biol Med. 1999;26(3-4):463–471. doi:10.1016/s0891-5849(98)00216-0.
  • Schriewer JM, Peek CB, Bass J, Schumacker PT. ROS-mediated PARP activity undermines mitochondrial function after permeability transition pore opening during myocardial ischemia-reperfusion. J Am Heart Assoc. 2013;2(2):e000159. doi:10.1161/JAHA.113.000159.
  • Hao T, Yu J, Wu Z, et al. Hypoxia-reprogramed megamitochondrion contacts and engulfs lysosome to mediate mitochondrial self-digestion. Nat Commun. 2023;14(1):4105. doi:10.1038/s41467-023-39811-9.
  • Liao S, Chen L, Song Z, He H. The fate of damaged mitochondrial DNA in the cell. Biochim Biophys Acta Mol Cell Res. 2022;1869(5):119233. doi:10.1016/j.bbamcr.2022.119233.
  • van der Toorn M, Sewer A, Marescotti D, et al. The biological effects of long-term exposure of human bronchial epithelial cells to total particulate matter from a candidate modified-risk tobacco product. Toxicol in Vitro. 2018;50:95–108. doi:10.1016/j.tiv.2018.02.019.
  • Walczak J, Malinska D, Drabik K, et al. Mitochondrial Network and Biogenesis in Response to Short and Long-Term Exposure of Human BEAS-2B Cells to Aerosol Extracts from the Tobacco Heating System 2.2. Cell Physiol Biochem. 2020;54:230–251.
  • Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–1033. doi:10.1126/science.1160809.
  • Cao X, Fu M, Bi R, et al. Cadmium induced BEAS-2B cells apoptosis and mitochondria damage via MAPK signaling pathway. Chemosphere. 2021;263:128346. doi:10.1016/j.chemosphere.2020.128346.
  • Mu M, Zhao H, Wang Y, Liu J, Fei D, Xing M. Arsenic trioxide or/and copper sulfate co-exposure induce glandular stomach of chicken injury via destruction of the mitochondrial dynamics and activation of apoptosis as well as autophagy. Ecotoxicol Environ Saf. 2019;185:109678. doi:10.1016/j.ecoenv.2019.109678.
  • Singh V, Singh N, Verma M, et al. Hexavalent-Chromium-Induced Oxidative Stress and the Protective Role of Antioxidants against Cellular Toxicity. Antioxidants (Basel). 2022;11(12):11. doi:10.3390/antiox11122375.
  • Feng M, Yin H, Peng H, Liu Z, Lu G, Dang Z. Hexavalent chromium induced oxidative stress and apoptosis in Pycnoporus sanguineus. Environ Pollut. 2017;228:128–139. doi:10.1016/j.envpol.2017.05.012.
  • Yu X, Yu RQ, Gui D, et al. Hexavalent chromium induces oxidative stress and mitochondria-mediated apoptosis in isolated skin fibroblasts of Indo-Pacific humpback dolphin. Aquat Toxicol. 2018;203:179–186. doi:10.1016/j.aquatox.2018.08.012.
  • Son YO, Hitron JA, Wang X, et al. Cr(VI) induces mitochondrial-mediated and caspase-dependent apoptosis through reactive oxygen species-mediated p53 activation in JB6 Cl41 cells. Toxicol Appl Pharmacol. 2010;245(2):226–235. doi:10.1016/j.taap.2010.03.004.
  • Russo P, Catassi A, Cesario A, et al. Molecular mechanisms of hexavalent chromium-induced apoptosis in human bronchoalveolar cells. Am J Respir Cell Mol Biol. 2005;33(6):589–600. doi:10.1165/rcmb.2005-0213OC.
  • Carlisle DL, Pritchard DE, Singh J, Patierno SR. Chromium(VI) induces p53-dependent apoptosis in diploid human lung and mouse dermal fibroblasts. Mol Carcinog. 2000;28(2):111–118. doi:10.1002/1098-2744(200006)28:2<111::AID-MC7>3.0.CO;2-Y.
  • Ye J, Wang S, Leonard SS, et al. Role of reactive oxygen species and p53 in chromium(VI)-induced apoptosis. J Biol Chem. 1999;274(49):34974–34980. doi:10.1074/jbc.274.49.34974.
  • Bagchi D, Bagchi M, Stohs SJ. Chromium (VI)-induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene. Mol Cell Biochem. 2001;222(1-2):149–158.
  • Fu SC, Liu JM, Lee KI, et al. Cr(VI) induces ROS-mediated mitochondrial-dependent apoptosis in neuronal cells via the activation of Akt/ERK/AMPK signaling pathway. Toxicol in Vitro. 2020;65:104795. doi:10.1016/j.tiv.2020.104795.
  • Wang L, Zheng P, Cui Y, et al. Regulation of Parkin in Cr (VI)-induced mitophagy in chicken hepatocytes. Ecotoxicol Environ Saf. 2022;248:114315. doi:10.1016/j.ecoenv.2022.114315.
  • Ma Y, Zhang Y, Xiao Y, Xiao F. Increased Mitochondrial Fragmentation Mediated by Dynamin-Related Protein 1 Contributes to Hexavalent Chromium-Induced Mitochondrial Respiratory Chain Complex I-Dependent Cytotoxicity. Toxics. 2020;8(3):8. doi:10.3390/toxics8030050.
  • Dlamini MB, Gao Z, Hasenbilige, Jiang L, Geng C, Li Q, Shi X, Liu Y, Cao J. The crosstalk between mitochondrial dysfunction and endoplasmic reticulum stress promoted ATF4-mediated mitophagy induced by hexavalent chromium. Environ Toxicol, 2021;36:1162–1172. doi:10.1002/tox.23115.
  • Zhang Y, Ma Y, Xiao Y, Lu C, Xiao F. Drp1-dependent mitochondrial fission contributes to Cr(VI)-induced mitophagy and hepatotoxicity. Ecotoxicol Environ Saf. 2020;203:110928. doi:10.1016/j.ecoenv.2020.110928.
  • Wang CC, Fang KM, Yang CS, Tzeng SF. Reactive oxygen species-induced cell death of rat primary astrocytes through mitochondria-mediated mechanism. J Cell Biochem. 2009;107(5):933–943. doi:10.1002/jcb.22196.
  • Zhang X, Wang Y, Chen M, Zeng M. Hexavalent chromium-induced apoptosis in Hep3B cells is accompanied by calcium overload, mitochondrial damage, and AIF translocation. Ecotoxicol Environ Saf. 2021;208:111391. doi:10.1016/j.ecoenv.2020.111391.
  • Xiao Y, Zeng M, Yin L, Li N, Xiao F. Clusterin increases mitochondrial respiratory chain complex I activity and protects against hexavalent chromium-induced cytotoxicity in L-02 hepatocytes. Toxicol Res (Camb). 2019;8(1):15–24. doi:10.1039/c8tx00231b.
  • Ryberg D, Alexander J. Mechanisms of chromium toxicity in mitochondria. Chem Biol Interact. 1990;75(2):141–151. doi:10.1016/0009-2797(90)90114-3.
  • Ryberg D, Alexander J. Inhibitory action of hexavalent chromium (Cr(VI)) on the mitochondrial respiration and a possible coupling to the reduction of Cr(VI). Biochem Pharmacol. 1984;33(15):2461–2466. doi:10.1016/0006-2952(84)90718-4.
  • Xiao F, Li Y, Luo L, et al. Role of mitochondrial electron transport chain dysfunction in Cr(VI)-induced cytotoxicity in L-02 hepatocytes. Cell Physiol Biochem. 2014;33(4):1013–1025. doi:10.1159/000358672.
  • Zhang Y, Ma Y, Liang N, Liang Y, Lu C, Xiao F. Blockage of ROS-ERK-DLP1 signaling and mitochondrial fission alleviates Cr(VI)-induced mitochondrial dysfunction in L02 hepatocytes. Ecotoxicol Environ Saf. 2019;186:109749. doi:10.1016/j.ecoenv.2019.109749.
  • Myers CR, Antholine WE, Myers JM. The pro-oxidant chromium(VI) inhibits mitochondrial complex I, complex II, and aconitase in the bronchial epithelium: EPR markers for Fe-S proteins. Free Radic Biol Med. 2010;49(12):1903–1915. doi:10.1016/j.freeradbiomed.2010.09.020.
  • Jasso-Chávez R, Pacheco-Rosales A, Lira-Silva E, Gallardo-Pérez JC, García N, Moreno-Sánchez R. Toxic effects of Cr(VI) and Cr(III) on energy metabolism of heterotrophic Euglena gracilis. Aquat Toxicol. 2010;100(4):329–338. doi:10.1016/j.aquatox.2010.08.006.
  • Fernandes MA, Santos MS, Alpoim MC, Madeira VM, Vicente JA. Chromium(VI) interaction with plant and animal mitochondrial bioenergetics: a comparative study. J Biochem Mol Toxicol. 2002;16(2):53–63. doi:10.1002/jbt.10025.
  • Xie Y, Zhuang ZX. Chromium (VI)-induced production of reactive oxygen species, change of plasma membrane potential and dissipation of mitochondria membrane potential in Chinese hamster lung cell cultures. Biomed Environ Sci. 2001;14(3):199–206.
  • Das J, Kang MH, Kim E, Kwon DN, Choi YJ, Kim JH. Hexavalent chromium induces apoptosis in male somatic and spermatogonial stem cells via redox imbalance. Sci Rep. 2015;5(1):13921. doi:10.1038/srep13921.
  • Lv Y, Zhang P, Guo J, et al. Melatonin protects mouse spermatogonial stem cells against hexavalent chromium-induced apoptosis and epigenetic histone modification. Toxicol Appl Pharmacol. 2018;340:30–38. doi:10.1016/j.taap.2017.12.017.
  • Wuri L, Arosh JA, Wu JZ, Banu SK. Exposure to hexavalent chromium causes infertility by disrupting cytoskeletal machinery and mitochondrial function of the metaphase II oocytes in superovulated rats. Toxicol Rep. 2022;9:219–229. doi:10.1016/j.toxrep.2022.02.002.
  • Li H, Shi J, Gao H, et al. Hexavalent Chromium Causes Apoptosis and Autophagy by Inducing Mitochondrial Dysfunction and Oxidative Stress in Broiler Cardiomyocytes. Biol Trace Elem Res. 2022;200(6):2866–2875. doi:10.1007/s12011-021-02877-x.
  • Wang Y, Hao J, Zhang S, et al. Inflammatory injury and mitophagy induced by Cr(VI) in chicken liver. Environ Sci Pollut Res Int. 2020;27(18):22980–22988. doi:10.1007/s11356-020-08544-3.
  • Zhong X, de Cássia da Silveira E Sá R, Zhong C. Mitochondrial Biogenesis in Response to Chromium (VI) Toxicity in Human Liver Cells. Int J Mol Sci. 2017;18(9):18.
  • Liang N, Li S, Liang Y, et al. Clusterin inhibits Cr(VI)-induced apoptosis via enhancing mitochondrial biogenesis through AKT-associated STAT3 activation in L02 hepatocytes. Ecotoxicol Environ Saf. 2021;221:112447. doi:10.1016/j.ecoenv.2021.112447.
  • Scott I, Youle RJ. Mitochondrial fission and fusion. Essays Biochem. 2010;47:85–98. doi:10.1042/bse0470085.
  • Yang Q, Han B, Xue J, et al. Hexavalent chromium induces mitochondrial dynamics disorder in rat liver by inhibiting AMPK/PGC-1alpha signaling pathway. Environ Pollut. 2020;265(Pt A):114855. doi:10.1016/j.envpol.2020.114855.
  • Xu Y, Wang X, Geng N, et al. Mitophagy is involved in chromium (VI)-induced mitochondria damage in DF-1 cells. Ecotoxicol Environ Saf. 2020;194:110414. doi:10.1016/j.ecoenv.2020.110414.
  • Wang Y, Wang L, Wang X, et al. Inflammatory Injury and Mitophagy in the Cock Heart Induced by the Oral Administration of Hexavalent Chromium. Biol Trace Elem Res. 2022;200(3):1312–1320. doi:10.1007/s12011-021-02715-0.
  • Gao Z, Mei J, Yan X, et al. Cr (VI) induced mitophagy via the interaction of HMGA2 and PARK2. Toxicol Lett. 2020;333:261–268. doi:10.1016/j.toxlet.2020.08.012.
  • Bao S, Zhang C, Luo S, et al. HMGA2 mediates Cr (VI)-induced metabolic reprogramming through binding to mitochondrial D-Loop region. Ecotoxicol Environ Saf. 2022;244:114085. doi:10.1016/j.ecoenv.2022.114085.
  • Lv Y, Li T, Yang M, et al. Melatonin Attenuates Chromium (VI)-Induced Spermatogonial Stem Cell/Progenitor Mitophagy by Restoration of METTL3-Mediated RNA N(6)-Methyladenosine Modification. Front Cell Dev Biol. 2021;9:684398. doi:10.3389/fcell.2021.684398.
  • Yuan Y, Ju YS, Kim Y, et al. Comprehensive molecular characterization of mitochondrial genomes in human cancers. Nat Genet. 2020;52(3):342–352. doi:10.1038/s41588-019-0557-x.
  • Lu J, Sharma LK, Bai Y. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis. Cell Res. 2009;19(7):802–815. doi:10.1038/cr.2009.69.
  • He ZF, Zheng LC, Xie DY, Yu SS, Zhao J. Mutational analysis of mitochondrial tRNA genes in patients with lung cancer. Balkan J Med Genet. 2016;19(2):45–50. doi:10.1515/bjmg-2016-0035.
  • Wang L, Chen ZJ, Zhang YK, Le HB. The role of mitochondrial tRNA mutations in lung cancer. Int J Clin Exp Med. 2015;8:13341–13346.
  • Delaunay S, Pascual G, Feng B, et al. Mitochondrial RNA modifications shape metabolic plasticity in metastasis. Nature. 2022;607(7919):593–603. doi:10.1038/s41586-022-04898-5.
  • Lin YH, Lim SN, Chen CY, Chi HC, Yeh CT, Lin WR. Functional Role of Mitochondrial DNA in Cancer Progression. Int J Mol Sci. 2022;23(3):23. doi:10.3390/ijms23031659.
  • Tiranti V, Rossi E, Ruiz-Carrillo A, et al. Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involved in mitochondrial biogenesis. Genomics. 1995;25(2):559–564. doi:10.1016/0888-7543(95)80058-t.
  • Zhang J, Simpson CM, Berner J, et al. Systematic identification of anticancer drug targets reveals a nucleus-to-mitochondria ROS-sensing pathway. Cell. 2023;186(11):2361–2379 e25. doi:10.1016/j.cell.2023.04.026.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.