Mfn2-mediated mitochondrial fusion alleviates doxorubicin-induced cardiotoxicity with enhancing its anticancer activity through metabolic switch

Hulst, 2021, Anthracyclines: biosynthesis, engineering and clinical applications, Nat. Prod. Rep. Cardinale, 2015, Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy, Circulation, 131, 1981, 10.1161/CIRCULATIONAHA.114.013777 Shaikh, 2016, Cardioprotection and second malignant neoplasms associated with dexrazoxane in children receiving anthracycline chemotherapy: a systematic review and meta-analysis, J. Natl. Cancer Inst., 108, 10.1093/jnci/djv357 Tebbi, 2007, Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease, J. Clin. Oncol., 25, 493, 10.1200/JCO.2005.02.3879 Hernandez-Resendiz, 2020, Targeting mitochondrial fusion and fission proteins for cardioprotection, J. Cell Mol. Med., 24, 6571, 10.1111/jcmm.15384 Ding, 2018, Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1α pathway, J. Pineal Res., 65, 10.1111/jpi.12491 Forte, 2021, Society of Cardiology Working group on, H. Molecular Biology of the, the role of mitochondrial dynamics in cardiovascular diseases, Br. J. Pharmacol., 178, 2060, 10.1111/bph.15068 Qin, 2020, Mitochondrial fusion mediated by fusion promotion and fission inhibition directs adult mouse heart function toward a different direction, Faseb. J., 34, 663, 10.1096/fj.201901671R Ong, 2010, Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury, Circulation, 121, 2012, 10.1161/CIRCULATIONAHA.109.906610 Ding, 2020, Mitochondrial fusion promoter restores mitochondrial dynamics balance and ameliorates diabetic cardiomyopathy in an optic atrophy 1-dependent way, Acta Physiol., 229, 10.1111/apha.13428 Si, 2020, Silibinin inhibits migration and invasion of breast cancer MDA-MB-231 cells through induction of mitochondrial fusion, Mol. Cell. Biochem., 463, 189, 10.1007/s11010-019-03640-6 Zhao, 2013, Mitochondrial dynamics regulates migration and invasion of breast cancer cells, Oncogene, 32, 4814, 10.1038/onc.2012.494 Zhang, 2020, FNDC5 alleviates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via activating AKT, Cell Death Differ., 27, 540, 10.1038/s41418-019-0372-z Fisher, 2005, Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity, Circulation, 111, 1601, 10.1161/01.CIR.0000160359.49478.C2 Sohal, 2001, Temporally regulated and tissue-specific gene manipulations in the adult and embryonic heart using a tamoxifen-inducible Cre protein, Circ. Res., 89, 20, 10.1161/hh1301.092687 Zepeda, 2014, Drp1 loss-of-function reduces cardiomyocyte oxygen dependence protecting the heart from ischemia-reperfusion injury, J. Cardiovasc. Pharmacol., 63, 477, 10.1097/FJC.0000000000000071 Shimizu, 2016, DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission, J. Mol. Cell. Cardiol., 97, 56, 10.1016/j.yjmcc.2016.04.008 Ji, 2010, Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress, Am. J. Physiol. Endocrinol. Metab., 298, E871, 10.1152/ajpendo.00623.2009 Fan, 2008, Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity, Circ. Res., 103, 1270, 10.1161/CIRCRESAHA.108.182832 Chen, 2017, A mix of apple pomace polysaccharide improves mitochondrial function and reduces oxidative stress in the liver of high-fat diet-induced obese mice, Mol. Nutr. Food Res., 61, 10.1002/mnfr.201600433 Fu, 2015, Direct evidence that myocardial insulin resistance following myocardial ischemia contributes to post-ischemic heart failure, Sci. Rep., 5, 17927, 10.1038/srep17927 Chen, 2016, MicroRNA-630 suppresses tumor metastasis through the TGF-β- miR-630-Slug signaling pathway and correlates inversely with poor prognosis in hepatocellular carcinoma, Oncotarget, 7, 22674, 10.18632/oncotarget.8047 Zhou, 2017, Foxo3a inhibits mitochondrial fission and protects against doxorubicin-induced cardiotoxicity by suppressing MIEF2, Free Radic. Biol. Med., 104, 360, 10.1016/j.freeradbiomed.2017.01.037 Wallace, 2020, Mitochondrial determinants of doxorubicin-induced cardiomyopathy, Circ. Res., 126, 926, 10.1161/CIRCRESAHA.119.314681 Wenningmann, 2019, Insights into doxorubicin-induced cardiotoxicity: molecular mechanisms, preventive strategies, and early monitoring, Mol. Pharmacol., 96, 219, 10.1124/mol.119.115725 Xia, 2020, Doxorubicin induces cardiomyocyte apoptosis and atrophy through cyclin-dependent kinase 2-mediated activation of forkhead box O1, J. Biol. Chem., 295, 4265, 10.1074/jbc.RA119.011571 Kuznetsov, 2021, Structural and functional remodeling of mitochondria as an adaptive response to energy deprivation, Biochim. Biophys. Acta Bioenerg., 1862, 10.1016/j.bbabio.2021.148393 Lunt, 2011, Aerobic glycolysis: meeting the metabolic requirements of cell proliferation, Annu. Rev. Cell Dev. Biol., 27, 441, 10.1146/annurev-cellbio-092910-154237 Rodrigues, 2020, Therapeutic potential of targeting mitochondrial dynamics in cancer, Biochem. Pharmacol., 182, 10.1016/j.bcp.2020.114282 Ong, 2013, Mitochondrial dynamics in cardiovascular health and disease, Antioxidants Redox Signal., 19, 400, 10.1089/ars.2012.4777 Gao, 2020, SIK2 promotes reprogramming of glucose metabolism through PI3K/AKT/HIF-1alpha pathway and Drp1-mediated mitochondrial fission in ovarian cancer, Cancer Lett., 469, 89, 10.1016/j.canlet.2019.10.029 Chen, 2017, Mitochondrial dynamics in regulating the unique phenotypes of cancer and stem cells, Cell Metabol., 26, 39, 10.1016/j.cmet.2017.05.016 Studneva, 2019, Protective effects of a novel agonist of galanin receptors against doxorubicin-induced cardiotoxicity in rats, Cardiovasc. Toxicol., 19, 136, 10.1007/s12012-018-9483-x Zhu, 2011, Dietary nitrate supplementation protects against Doxorubicin-induced cardiomyopathy by improving mitochondrial function, J. Am. Coll. Cardiol., 57, 2181, 10.1016/j.jacc.2011.01.024 Cova, 1992, Subcellular distribution of two spin trapping agents in rat heart: possible explanation for their different protective effects against doxorubicin-induced cardiotoxicity, Free Radic. Res. Commun., 15, 353, 10.3109/10715769209049151 Doroshow, 1986, Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical, J. Biol. Chem., 261, 3068, 10.1016/S0021-9258(17)35747-2 Davies, 1986, Redox cycling of anthracyclines by cardiac mitochondria. I. Anthracycline radical formation by NADH dehydrogenase, J. Biol. Chem., 261, 3060, 10.1016/S0021-9258(17)35746-0 Zhang, 2012, Identification of the molecular basis of doxorubicin-induced cardiotoxicity, Nat. Med., 18, 1639, 10.1038/nm.2919 Catanzaro, 2019, Doxorubicin-induced cardiomyocyte death is mediated by unchecked mitochondrial fission and mitophagy, Faseb. J., 10.1096/fj.201802663R Tang, 2017, Doxorubicin-induced cardiomyocyte apoptosis: role of mitofusin 2, Int. J. Biochem. Cell Biol., 88, 55, 10.1016/j.biocel.2017.05.006 Li, 2014, Mitofusin 1 is negatively regulated by microRNA 140 in cardiomyocyte apoptosis, Mol. Cell Biol., 34, 1788, 10.1128/MCB.00774-13 Dorn, 2020, 2nd, Mitofusins as mitochondrial anchors and tethers, J. Mol. Cell. Cardiol., 142, 146, 10.1016/j.yjmcc.2020.04.016 Chen, 2013, 2nd, PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria, Science, 340, 471, 10.1126/science.1231031 Wu, 2019, Mitochondria-associated endoplasmic reticulum membranes in the heart, Arch. Biochem. Biophys., 662, 201, 10.1016/j.abb.2018.12.018 Tong, 2020, The role of Drp1 in mitophagy and cell death in the heart, J. Mol. Cell. Cardiol., 142, 138, 10.1016/j.yjmcc.2020.04.015 Schrepfer, 2016, Mitofusins, from mitochondria to metabolism, Mol. Cell, 61, 683, 10.1016/j.molcel.2016.02.022 Guo, 2014, QKI deficiency promotes FoxO1 mediated nitrosative stress and endoplasmic reticulum stress contributing to increased vulnerability to ischemic injury in diabetic heart, J. Mol. Cell. Cardiol., 75, 131, 10.1016/j.yjmcc.2014.07.010 Battiprolu, 2012, Metabolic stress-induced activation of FoxO1 triggers diabetic cardiomyopathy in mice, J. Clin. Invest., 122, 1109, 10.1172/JCI60329 Shi, 2018, FOXO1 inhibition potentiates endothelial angiogenic functions in diabetes via suppression of ROCK1/Drp1-mediated mitochondrial fission, Biochim. Biophys. Acta (BBA) - Mol. Basis Dis., 1864, 2481, 10.1016/j.bbadis.2018.04.005 Filadi, 2018, Mitofusin 2: from functions to disease, Cell Death Dis., 9, 330, 10.1038/s41419-017-0023-6 Allegra, 2019, Relationship between mitofusin 2 and cancer, Adv. Protein Chem. Struct. Biol., 116, 209, 10.1016/bs.apcsb.2018.11.009