{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:53:29Z","timestamp":1787226809033,"version":"build-2736575974"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T00:00:00Z","timestamp":1574121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31600653"],"award-info":[{"award-number":["31600653"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571455"],"award-info":[{"award-number":["31571455"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31570809"],"award-info":[{"award-number":["31570809"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31401210"],"award-info":[{"award-number":["31401210"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["51403104"],"award-info":[{"award-number":["51403104"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In recent years, copper complexes have gradually become the focus of potential anticancer drugs due to their available redox properties and low toxicity. In this study, a novel mitochondrion-targeting copper (II) complex, [Cu (ttpy-tpp)Br<jats:sub>2<\/jats:sub>] Br (simplified as CTB), is first synthesized by our group. CTB with tri-phenyl-phosphine (TPP), a targeting and lipophilic group, can cross the cytoplasmic and mitochondrial membranes of tumor cells. The present study aims to investigate how CTB affects mitochondrial functions and exerts its anti-tumor activity in hepatoma cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Multiple molecular experiments including Flow cytometry, Western blot, Immunofluorescence, Tracker staining, Transmission Electron Microscopy and Molecular docking simulation were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>CTB induced apoptosis via collapse of mitochondrial membrane potential (MMP), ROS production, Bax mitochondrial aggregation as well as cytochrome c release, indicating that CTB-induced apoptosis was associated with mitochondrial pathway in human hepatoma cells. Mechanistic study revealed that ROS-related mitochondrial translocation of p53 was involved in CTB-mediated apoptosis. Simultaneously, elevated mitochondrial Drp1 levels were also observed, and interruption of Drp1 activation played critical role in p53-dependent apoptosis. CTB also strongly suppressed the growth of liver cancer xenografts in vivo.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In human hepatoma cells, CTB primarily induces mitochondrial dysfunction and promotes accumulation of ROS, leading to activation of Drp1. These stimulation signals accelerate mitochondrial accumulation of p53 and lead to the eventual apoptosis. Our research shows that CTB merits further evaluation as a chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12964-019-0468-6","type":"journal-article","created":{"date-parts":[[2019,11,19]],"date-time":"2019-11-19T07:01:44Z","timestamp":1574146904000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1"],"prefix":"10.1186","volume":"17","author":[{"given":"Jiangjuan","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaochen","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanzhong","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7092-7843","authenticated-orcid":false,"given":"Shizhong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,19]]},"reference":[{"key":"468_CR1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jhep.2015.08.028","volume":"64","author":"U Saran","year":"2016","unstructured":"Saran U, Humar B, Kolly P, et al. Hepatocellular carcinoma and lifestyles. J Hepatol. 2016;64:203\u201314.","journal-title":"J Hepatol"},{"key":"468_CR2","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1002\/hep.28998","volume":"65","author":"U Cillo","year":"2017","unstructured":"Cillo U, Vitale A, Polacco M, et al. Liver transplantation for hepatocellular carcinoma through the lens of transplant benefit. Hepatology. 2017;65:1741\u20138.","journal-title":"Hepatology"},{"key":"468_CR3","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1016\/j.jhep.2016.09.012","volume":"66","author":"A Vitale","year":"2017","unstructured":"Vitale A, Peck-Radosavljevic M, Giannini EG, et al. Personalized treatment of patients with very early hepatocellular carcinoma. J Hepatol. 2017;66:412\u201323.","journal-title":"J Hepatol"},{"key":"468_CR4","doi-asserted-by":"publisher","first-page":"599","DOI":"10.2147\/DDDT.S119488","volume":"11","author":"U Ndagi","year":"2017","unstructured":"Ndagi U, Mhlongo N, Soliman ME. Metal complexes in cancer therapy - an update from drug design perspective. Drug Des Devel Ther. 2017;11:599\u2013616.","journal-title":"Drug Des Devel Ther"},{"key":"468_CR5","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.biomaterials.2017.06.007","volume":"139","author":"JX Fan","year":"2017","unstructured":"Fan JX, Zheng DW, Rong L, et al. Targeting epithelial-mesenchymal transition: metal organic network nano-complexes for preventing tumor metastasis. Biomaterials. 2017;139:116\u201326.","journal-title":"Biomaterials"},{"key":"468_CR6","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.cbpa.2017.10.014","volume":"43","author":"T Zou","year":"2018","unstructured":"Zou T, Lok CN, Wan PK, et al. Anticancer metal-N-heterocyclic carbene complexes of gold, platinum and palladium. Curr Opin Chem Biol. 2018;43:30\u20136.","journal-title":"Curr Opin Chem Biol"},{"key":"468_CR7","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/chem.201604792","volume":"23","author":"LK McKenzie","year":"2017","unstructured":"McKenzie LK, Sazanovich IV, Baggaley E, et al. Metal complexes for two-photon photodynamic therapy: a Cyclometallated iridium complex induces two-photon photosensitization of Cancer cells under near-IR light. Chemistry. 2017;23:234\u20138.","journal-title":"Chemistry"},{"key":"468_CR8","unstructured":"Denoyer D, Clatworthy SAS, Cater MA. Copper complexes in Cancer therapy. Met Ions Life Sci. 2018;18:469\u2013506."},{"key":"468_CR9","doi-asserted-by":"publisher","first-page":"11801","DOI":"10.1021\/acs.inorgchem.6b01884","volume":"55","author":"SM Leite","year":"2016","unstructured":"Leite SM, Lima LM, Gama S, et al. Copper (II) complexes of Phenanthroline and Histidine containing ligands: synthesis, characterization and evaluation of their DNA cleavage and cytotoxic activity. Inorg Chem. 2016;55:11801\u201314.","journal-title":"Inorg Chem"},{"key":"468_CR10","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.molcel.2015.12.002","volume":"61","author":"I Martinez-Reyes","year":"2016","unstructured":"Martinez-Reyes I, Diebold LP, Kong H, et al. TCA cycle and mitochondrial membrane potential are necessary for diverse biological functions. Mol Cell. 2016;61:199\u2013209.","journal-title":"Mol Cell"},{"key":"468_CR11","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.semcancer.2017.06.006","volume":"47","author":"HK Kim","year":"2017","unstructured":"Kim HK, Noh YH, Nilius B, et al. Current and upcoming mitochondrial targets for cancer therapy. Semin Cancer Biol. 2017;47:154\u201367.","journal-title":"Semin Cancer Biol"},{"key":"468_CR12","doi-asserted-by":"publisher","first-page":"2640","DOI":"10.1021\/mp500038g","volume":"11","author":"M Han","year":"2014","unstructured":"Han M, Vakili MR, Soleymani Abyaneh H, et al. Mitochondrial delivery of doxorubicin via triphenylphosphine modification for overcoming drug resistance in MDA-MB-435\/DOX cells. Mol Pharm. 2014;11:2640\u20139.","journal-title":"Mol Pharm"},{"key":"468_CR13","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/978-1-4939-2288-8_5","volume":"1265","author":"DY Kim","year":"2015","unstructured":"Kim DY, Min JJ. Synthesis and evaluation of (1)(8) F-labeled fluoroalkyl triphenylphosphonium salts as mitochondrial voltage sensors in PET myocardial imaging. Methods Mol Biol. 2015;1265:59\u201372.","journal-title":"Methods Mol Biol"},{"key":"468_CR14","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.taap.2016.08.018","volume":"309","author":"C Sandoval-Acuna","year":"2016","unstructured":"Sandoval-Acuna C, Fuentes-Retamal S, Guzman-Rivera D, et al. Destabilization of mitochondrial functions as a target against breast cancer progression: role of TPP(+)-linked- polyhydroxybenzoates. Toxicol Appl Pharmacol. 2016;309:2\u201314.","journal-title":"Toxicol Appl Pharmacol"},{"key":"468_CR15","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1021\/bc8002056","volume":"19","author":"CT Yang","year":"2008","unstructured":"Yang CT, Kim YS, Wang J, et al. 64Cu-labeled 2-(diphenylphosphoryl) ethyldiphenylphosphonium cations as highly selective tumor imaging agents: effects of linkers and chelates on radiotracer biodistribution characteristics. Bioconjug Chem. 2008;19:2008\u201322.","journal-title":"Bioconjug Chem"},{"key":"468_CR16","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1039\/C4SC00384E","volume":"5","author":"W Zhou","year":"2014","unstructured":"Zhou W, Wang XY, Hu M, et al. A mitochondrion-targeting copper complex exhibits potent cytotoxicity against cisplatin-resistant tumor cells through multiple mechanisms of action. Chem Sci. 2014;5:2761\u201370.","journal-title":"Chem Sci"},{"key":"468_CR17","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1080\/10715762.2017.1407412","volume":"52","author":"W Lee","year":"2018","unstructured":"Lee W, Lee DG. Reactive oxygen species modulate itraconazole-induced apoptosis via mitochondrial disruption in Candida albicans. Free Radic Res. 2018;52:39\u201350.","journal-title":"Free Radic Res"},{"key":"468_CR18","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/cdd.2017.169","volume":"25","author":"BJ Aubrey","year":"2018","unstructured":"Aubrey BJ, Kelly GL, Janic A, et al. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018;25:104\u201313.","journal-title":"Cell Death Differ"},{"key":"468_CR19","doi-asserted-by":"publisher","first-page":"e2266","DOI":"10.1038\/cddis.2016.167","volume":"7","author":"J Zhang","year":"2016","unstructured":"Zhang J, Huang K, O'Neill KL, et al. Bax\/Bak activation in the absence of bid, Bim, Puma, and p53. Cell Death Dis. 2016;7:e2266.","journal-title":"Cell Death Dis"},{"key":"468_CR20","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/febs.14186","volume":"285","author":"A Pena-Blanco","year":"2018","unstructured":"Pena-Blanco A, Garcia-Saez AJ. Bax, Bak and beyond - mitochondrial performance in apoptosis. FEBS J. 2018;285:416\u201331.","journal-title":"FEBS J"},{"key":"468_CR21","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1038\/cdd.2013.186","volume":"21","author":"Y Shi","year":"2014","unstructured":"Shi Y, Nikulenkov F, Zawacka-Pankau J, et al. ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell Death Differ. 2014;21:612\u201323.","journal-title":"Cell Death Differ"},{"key":"468_CR22","doi-asserted-by":"publisher","first-page":"1788","DOI":"10.1038\/s41388-017-0103-1","volume":"37","author":"S NavaneethaKrishnan","year":"2018","unstructured":"NavaneethaKrishnan S, Rosales JL, Lee KY. Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through dysregulation of the mitochondrial permeability transition pore. Oncogene. 2018;37:1788\u2013804.","journal-title":"Oncogene"},{"key":"468_CR23","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.freeradbiomed.2015.11.022","volume":"90","author":"Y Mi","year":"2016","unstructured":"Mi Y, Xiao C, Du Q, et al. Momordin Ic couples apoptosis with autophagy in human hepatoblastoma cancer cells by reactive oxygen species (ROS)-mediated PI3K\/Akt and MAPK signaling pathways. Free Radic Biol Med. 2016;90:230\u201342.","journal-title":"Free Radic Biol Med"},{"key":"468_CR24","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/cdd.2016.117","volume":"24","author":"M Charni","year":"2017","unstructured":"Charni M, Aloni-Grinstein R, Molchadsky A, et al. p53 on the crossroad between regeneration and cancer. Cell Death Differ. 2017;24:8\u201314.","journal-title":"Cell Death Differ"},{"key":"468_CR25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jep.2013.10.042","volume":"151","author":"R Lan","year":"2014","unstructured":"Lan R, Zhang Y, Xiang J, et al. Xiao-Xu-Ming decoction preserves mitochondrial integrity and reduces apoptosis after focal cerebral ischemia and reperfusion via the mitochondrial p53 pathway. J Ethnopharmacol. 2014;151:307\u201316.","journal-title":"J Ethnopharmacol"},{"key":"468_CR26","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s10863-016-9669-5","volume":"48","author":"CQ Dai","year":"2016","unstructured":"Dai CQ, Luo TT, Luo SC, et al. p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases. J Bioenerg Biomembr. 2016;48:337\u201347.","journal-title":"J Bioenerg Biomembr"},{"key":"468_CR27","doi-asserted-by":"publisher","first-page":"2818","DOI":"10.1002\/bit.26407","volume":"114","author":"N Noda","year":"2017","unstructured":"Noda N, Awais R, Sutton R, et al. Dynamic monitoring of p53 translocation to mitochondria for the analysis of specific inhibitors using luciferase-fragment complementation. Biotechnol Bioeng. 2017;114:2818\u201327.","journal-title":"Biotechnol Bioeng"},{"key":"468_CR28","doi-asserted-by":"publisher","first-page":"8073721","DOI":"10.1155\/2017\/8073721","volume":"2017","author":"J Prieto","year":"2017","unstructured":"Prieto J, Torres J. Mitochondrial dynamics: in cell reprogramming as it is in Cancer. Stem Cells Int. 2017;2017:8073721.","journal-title":"Stem Cells Int"},{"key":"468_CR29","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1113\/JP271301","volume":"594","author":"C Vasquez-Trincado","year":"2016","unstructured":"Vasquez-Trincado C, Garcia-Carvajal I, Pennanen C, et al. Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol. 2016;594:509\u201325.","journal-title":"J Physiol"},{"key":"468_CR30","first-page":"602","volume":"2017","author":"S Srinivasan","year":"1858","unstructured":"Srinivasan S, Guha M, Kashina A, et al. Mitochondrial dysfunction and mitochondrial dynamics-the cancer connection. Biochim Biophys Acta. 1858;2017:602\u201314.","journal-title":"Biochim Biophys Acta"},{"key":"468_CR31","doi-asserted-by":"publisher","first-page":"R207","DOI":"10.1016\/j.cub.2016.01.009","volume":"26","author":"J Prudent","year":"2016","unstructured":"Prudent J, McBride HM. Mitochondrial dynamics: ER actin tightens the Drp1 noose. Curr Biol. 2016;26:R207\u20139.","journal-title":"Curr Biol"},{"key":"468_CR32","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.bbrc.2016.05.038","volume":"475","author":"M Roy","year":"2016","unstructured":"Roy M, Itoh K, Iijima M, et al. Parkin suppresses Drp1-independent mitochondrial division. Biochem Biophys Res Commun. 2016;475:283\u20138.","journal-title":"Biochem Biophys Res Commun"},{"key":"468_CR33","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.redox.2017.02.020","volume":"12","author":"X Yang","year":"2017","unstructured":"Yang X, Wang H, Ni HM, et al. Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice. Redox Biol. 2017;12:264\u201373.","journal-title":"Redox Biol"},{"key":"468_CR34","first-page":"1267","volume":"2016","author":"B Oettinghaus","year":"1857","unstructured":"Oettinghaus B, D'Alonzo D, Barbieri E, et al. DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress. Biochim Biophys Acta. 1857;2016:1267\u201376.","journal-title":"Biochim Biophys Acta"},{"key":"468_CR35","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1016\/j.cell.2016.11.047","volume":"167","author":"J Yuan","year":"2016","unstructured":"Yuan J, Najafov A, Py BF. Roles of Caspases in necrotic cell death. Cell. 2016;167:1693\u2013704.","journal-title":"Cell"},{"key":"468_CR36","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s13402-018-0398-0","volume":"41","author":"P Sharma","year":"2018","unstructured":"Sharma P, Kumar S. Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: pivotal role of superoxide dismutase (SOD). Cell Oncol (Dordr). 2018;41:637\u201350.","journal-title":"Cell Oncol (Dordr)"},{"key":"468_CR37","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s12876-018-0761-7","volume":"18","author":"T Senoo","year":"2018","unstructured":"Senoo T, Sasaki R, Akazawa Y, et al. Geranylgeranylacetone attenuates fibrogenic activity and induces apoptosis in cultured human hepatic stellate cells and reduces liver fibrosis in carbon tetrachloride-treated mice. BMC Gastroenterol. 2018;18:34.","journal-title":"BMC Gastroenterol"},{"key":"468_CR38","doi-asserted-by":"publisher","first-page":"198","DOI":"10.7150\/ijbs.13716","volume":"12","author":"W Yu","year":"2016","unstructured":"Yu W, Zhang X, Liu J, et al. Cyclosporine a suppressed glucose oxidase induced P53 mitochondrial translocation and hepatic cell apoptosis through blocking mitochondrial permeability transition. Int J Biol Sci. 2016;12:198\u2013209.","journal-title":"Int J Biol Sci"},{"key":"468_CR39","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.cbpa.2009.11.015","volume":"14","author":"CM Che","year":"2010","unstructured":"Che CM, Siu FM. Metal complexes in medicine with a focus on enzyme inhibition. Curr Opin Chem Biol. 2010;14:255\u201361.","journal-title":"Curr Opin Chem Biol"},{"key":"468_CR40","first-page":"117","volume":"2018","author":"K Niedzwiecka","year":"1865","unstructured":"Niedzwiecka K, Tisi R, Penna S, et al. Two mutations in mitochondrial ATP6 gene of ATP synthase, related to human cancer, affect ROS, calcium homeostasis and mitochondrial permeability transition in yeast. Biochim Biophys Acta. 1865;2018:117\u201331.","journal-title":"Biochim Biophys Acta"},{"key":"468_CR41","first-page":"381","volume":"9","author":"K Anvari","year":"2012","unstructured":"Anvari K, Seilanian Toussi M, Kalantari M, et al. Expression of Bcl-2 and Bax in advanced or metastatic prostate carcinoma. Urol J. 2012;9:381\u20138.","journal-title":"Urol J"},{"key":"468_CR42","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.bbrc.2010.02.163","volume":"396","author":"E Norberg","year":"2010","unstructured":"Norberg E, Orrenius S, Zhivotovsky B. Mitochondrial regulation of cell death: processing of apoptosis-inducing factor (AIF). Biochem Biophys Res Commun. 2010;396:95\u2013100.","journal-title":"Biochem Biophys Res Commun"},{"key":"468_CR43","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.foodchem.2017.04.185","volume":"234","author":"LL Wang","year":"2017","unstructured":"Wang LL, Han L, Ma XL, et al. Effect of mitochondrial apoptotic activation through the mitochondrial membrane permeability transition pore on yak meat tenderness during postmortem aging. Food Chem. 2017;234:323\u201331.","journal-title":"Food Chem"},{"key":"468_CR44","doi-asserted-by":"publisher","first-page":"36803","DOI":"10.1074\/jbc.M405297200","volume":"279","author":"ME Soriano","year":"2004","unstructured":"Soriano ME, Nicolosi L, Bernardi P. Desensitization of the permeability transition pore by cyclosporin a prevents activation of the mitochondrial apoptotic pathway and liver damage by tumor necrosis factor-alpha. J Biol Chem. 2004;279:36803\u20138.","journal-title":"J Biol Chem"},{"key":"468_CR45","doi-asserted-by":"publisher","first-page":"7684","DOI":"10.1128\/JVI.00583-16","volume":"90","author":"Y Zhuang","year":"2016","unstructured":"Zhuang Y, Berens-Norman HM, Leser JS, et al. Mitochondrial p53 contributes to Reovirus-induced neuronal apoptosis and central nervous system injury in a mouse model of viral encephalitis. J Virol. 2016;90:7684\u201391.","journal-title":"J Virol"},{"key":"468_CR46","doi-asserted-by":"publisher","first-page":"102","DOI":"10.3389\/fonc.2017.00102","volume":"7","author":"D Pendin","year":"2017","unstructured":"Pendin D, Filadi R, Pizzo P. The concerted action of mitochondrial dynamics and positioning: new characters in Cancer onset and progression. Front Oncol. 2017;7:102.","journal-title":"Front Oncol"},{"key":"468_CR47","doi-asserted-by":"publisher","first-page":"e2886","DOI":"10.1038\/cddis.2017.255","volume":"8","author":"Z Zhang","year":"2017","unstructured":"Zhang Z, Yao Z, Zhao S, et al. Interaction between autophagy and senescence is required for dihydroartemisinin to alleviate liver fibrosis. Cell Death Dis. 2017;8:e2886.","journal-title":"Cell Death Dis"},{"key":"468_CR48","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.devcel.2007.11.019","volume":"14","author":"A Cassidy-Stone","year":"2008","unstructured":"Cassidy-Stone A, Chipuk JE, Ingerman E, et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax\/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008;14:193\u2013204.","journal-title":"Dev Cell"},{"key":"468_CR49","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1161\/CIRCULATIONAHA.111.036178","volume":"124","author":"SE Altin","year":"2011","unstructured":"Altin SE, Schulze PC. p53-upregulated modulator of apoptosis (PUMA): a novel proapoptotic molecule in the failing heart. Circulation. 2011;124:7\u20138.","journal-title":"Circulation"},{"issue":"5","key":"468_CR50","doi-asserted-by":"publisher","first-page":"F798","DOI":"10.1152\/ajprenal.00055.2017","volume":"314","author":"Yanggang Yuan","year":"2018","unstructured":"Yuan Y, Zhang A, Qi J, et al. P53\/Drp1-dependent mitochondrial fission mediates aldosterone-induced podocyte injury and mitochondrial dysfunction. Am J Physiol Renal Physiol. 2017. https:\/\/doi.org\/10.1152\/ajprenal.00055.2017.","journal-title":"American Journal of Physiology-Renal Physiology"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-019-0468-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12964-019-0468-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-019-0468-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T03:54:29Z","timestamp":1605671669000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-019-0468-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,19]]},"references-count":50,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["468"],"URL":"https:\/\/doi.org\/10.1186\/s12964-019-0468-6","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,19]]},"assertion":[{"value":"8 March 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experimental procedures were approved by the ethical review board of Nanjing University of Chinese Medicine (Nanjing, China).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors have read and approved the manuscript, its content, and its publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"149"}}