{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:24:03Z","timestamp":1792801443981,"version":"4.5.0"},"reference-count":121,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2019,5,11]],"date-time":"2019-05-11T00:00:00Z","timestamp":1557532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Mitochondrial function declines with age, leading to a variety of age-related diseases (metabolic, central nervous system-related, cancer, etc.) and medication usage increases with age due to the increase in diseases. Drug-induced mitochondrial toxicity has been described for many different drug classes and can lead to liver, muscle, kidney and central nervous system injury and, in rare cases, to death. Many of the most prescribed medications in the geriatric population carry mitochondrial liabilities. We have demonstrated that, over the past decade, each class of drugs that demonstrated mitochondrial toxicity contained drugs with both more and less adverse effects on mitochondria. As patient treatment is often essential, we suggest using medication(s) with the best safety profile and the avoidance of concurrent usage of multiple medications that carry mitochondrial liabilities. In addition, we also recommend lifestyle changes to further improve one\u2019s mitochondrial function, such as weight loss, exercise and nutrition.<\/jats:p>","DOI":"10.3390\/biology8020032","type":"journal-article","created":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T05:35:39Z","timestamp":1557725739000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Drug-Induced Mitochondrial Toxicity in the Geriatric Population: Challenges and Future Directions"],"prefix":"10.3390","volume":"8","author":[{"given":"Yvonne","family":"Will","sequence":"first","affiliation":[{"name":"SCIENTIA LLC, Ledyard, CT 06339, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefry E.","family":"Shields","sequence":"additional","affiliation":[{"name":"SCIENTIA LLC, Ledyard, CT 06339, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall B.","family":"Wallace","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1080\/07853890510007368","article-title":"Mitochondrial DNA and disease","volume":"37","author":"Dimauro","year":"2005","journal-title":"Ann. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.bbagen.2013.11.007","article-title":"Mitochondrial dysfunction and complications associated with diabetes","volume":"1840","author":"Blake","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Peng, K.Y., Watt, M.J., Rensen, S., Greve, J.W., Huynh, K., Jayawardana, K.S., Meikle, P.J., and Meex, R.C.R. (2018). Mitochondrial dysfunction-related lipid changes occur in non-alcoholic fatty liver disease progression. J. Lipid Res.","DOI":"10.1194\/jlr.M085613"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41569-018-0074-0","article-title":"Targeting mitochondria for cardiovascular disorders: Therapeutic potential and obstacles","volume":"16","author":"Bonora","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/978-3-319-55330-6_24","article-title":"Mitochondrial Dysfunction in Cardiovascular Aging","volume":"982","author":"Hoppel","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1111\/jnc.14037","article-title":"Brain aging and neurodegeneration: From a mitochondrial point of view","volume":"143","author":"Grimm","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1111\/fcp.12359","article-title":"Significance of mitochondria on cardiometabolic syndromes","volume":"32","author":"Anupama","year":"2018","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1042\/BST20170501","article-title":"Mitochondrial abnormalities in Parkinson\u2019s disease and Alzheimer\u2019s disease: Can mitochondria be targeted therapeutically?","volume":"46","author":"Macdonald","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3389\/fnins.2018.00342","article-title":"Mitochondrial Quality Control in Neurodegenerative Diseases: Focus on Parkinson\u2019s Disease and Huntington\u2019s Disease","volume":"12","author":"Vila","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.2147\/TCRM.S117491","article-title":"The potential role for use of mitochondrial DNA copy number as predictive biomarker in presbycusis","volume":"12","author":"Falah","year":"2016","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4355","DOI":"10.1167\/iovs.18-24938","article-title":"A Metabolomics Profiling of Glaucoma Points to Mitochondrial Dysfunction, Senescence, and Polyamines Deficiency","volume":"59","author":"Leruez","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.freeradbiomed.2018.08.038","article-title":"Reactive Oxygen Species, Aging and Articular Cartilage Homeostasis","volume":"132","author":"Bolduc","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ng Kee Kwong, F., Nicholson, A.G., Harrison, C.L., Hansbro, P.M., Adcock, I.M., and Chung, K.F. (2017). Is mitochondrial dysfunction a driving mechanism linking COPD to nonsmall cell lung carcinoma?. Eur. Respir. Rev., 26.","DOI":"10.1183\/16000617.0040-2017"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1172\/JCI120844","article-title":"Emerging evidence for targeting mitochondrial metabolic dysfunction in cancer therapy","volume":"128","author":"Zhu","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1249\/JES.0000000000000101","article-title":"Mitochondria Initiate and Regulate Sarcopenia","volume":"45","author":"Always","year":"2017","journal-title":"Exerc. Sport Sci. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hara, H., Kuwano, K., and Araya, J. (2018). Mitochondrial Quality Control in COPD and IPF. Cells, 7.","DOI":"10.3390\/cells7080086"},{"key":"ref_17","unstructured":"Raymond, P. (1928). The Rate of Living, Johns Hopkins University."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s00424-009-0724-5","article-title":"Mitochondrial function as a determinant of life span","volume":"459","author":"Lanza","year":"2010","journal-title":"Pflugers Arch."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.cell.2016.07.031","article-title":"Metabolic Control of Longevity","volume":"166","author":"Galluzzi","year":"2016","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.exger.2010.03.014","article-title":"How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis)","volume":"45","author":"Ristow","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1469-7793.2000.t01-1-00203.x","article-title":"Oxidative capacity and ageing in human muscle","volume":"526","author":"Conley","year":"2000","journal-title":"J. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.1073\/pnas.0501559102","article-title":"Decline in skeletal muscle mitochondrial function with aging in humans","volume":"102","author":"Short","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1532-5415.1972.tb00787.x","article-title":"The biological clock: The mitochondria?","volume":"20","author":"Harman","year":"1972","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A theory based on free radical and radiation chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. Gerontol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/BF02432509","article-title":"Free radical theory of aging: Consequences of mitochondrial aging","volume":"6","author":"Harman","year":"1983","journal-title":"Age"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"238463","DOI":"10.1155\/2014\/238463","article-title":"Mitochondrial aging and age-related dysfunction of mitochondria","volume":"2014","author":"Chistiakov","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/geronj\/23.4.454","article-title":"Age changes in size and number of mitochondria of human hepatic cells","volume":"23","author":"Tauchi","year":"1968","journal-title":"J. Gerontol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.mad.2016.12.005","article-title":"Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity","volume":"162","year":"2017","journal-title":"Mech. Ageing Dev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1152\/japplphysiol.01061.2002","article-title":"Reduced amount of mitochondrial DNA in aged human muscle","volume":"94","author":"Welle","year":"2003","journal-title":"J. Appl. Physiol. (1985)"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1146\/annurev-biochem-060408-093701","article-title":"Somatic mitochondrial DNA mutations in mammalian aging","volume":"79","author":"Larsson","year":"2010","journal-title":"Annu. Rev. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1172\/JCI64125","article-title":"The role of mitochondria in aging","volume":"123","author":"Bratic","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2933","DOI":"10.2337\/db08-0349","article-title":"Endurance exercise as a countermeasure for aging","volume":"57","author":"Lanza","year":"2008","journal-title":"Diabetes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0047-6374(84)90074-5","article-title":"Lowered rates of protein synthesis by mitochondria isolated from organisms of increasing age","volume":"24","author":"Bailey","year":"1984","journal-title":"Mech. Ageing Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/0531-5565(82)90033-X","article-title":"Age-related decline in the biosynthesis of mitochondrial inner membrane proteins","volume":"17","author":"Marcus","year":"1982","journal-title":"Exp. Gerontol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15364","DOI":"10.1073\/pnas.93.26.15364","article-title":"Effect of age on in vivo rates of mitochondrial protein synthesis in human skeletal muscle","volume":"93","author":"Rooyackers","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1042\/cs0910475","article-title":"Mitochondrial protein content and in vivo synthesis rates in skeletal muscle from critically ill rats","volume":"91","author":"Rooyackers","year":"1996","journal-title":"Clin. Sci. (Lond.)"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/j.mad.2010.07.003","article-title":"Signaling pathways in mitochondrial dysfunction and aging","volume":"131","author":"Mammucari","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.bbamcr.2011.01.029","article-title":"Mitochondrial longevity pathways","volume":"1813","author":"Vendelbo","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature14300","article-title":"Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans","volume":"521","author":"Palikaras","year":"2015","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1038\/sj.emboj.7601972","article-title":"Quality control of mitochondria: Protection against neurodegeneration and ageing","volume":"27","author":"Tatsuta","year":"2008","journal-title":"EMBO J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aac4854","article-title":"NAD(+) in aging, metabolism, and neurodegeneration","volume":"350","author":"Verdin","year":"2015","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.cell.2013.11.037","article-title":"Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging","volume":"155","author":"Gomes","year":"2013","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.cmet.2013.08.018","article-title":"Sestrins orchestrate cellular metabolism to attenuate aging","volume":"18","author":"Lee","year":"2013","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.cell.2013.05.027","article-title":"SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-62703-637-5_1","article-title":"Introduction: Sirtuins in aging and diseases","volume":"1077","author":"Guarente","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/j.1474-9726.2007.00347.x","article-title":"Mitochondrial function and apoptotic susceptibility in aging skeletal muscle","volume":"7","author":"Chabi","year":"2008","journal-title":"Aging Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.exger.2010.03.018","article-title":"Impaired quality control of mitochondria: Aging from a new perspective","volume":"45","author":"Weber","year":"2010","journal-title":"Exp. Gerontol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1517\/17425255.2014.939628","article-title":"Mitochondrial toxicity assessment in industry--a decade of technology development and insight","volume":"10","author":"Will","year":"2014","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2.20.1","DOI":"10.1002\/0471140856.tx0220s49","article-title":"Assessment of mitochondrial toxicity in HepG2 cells cultured in high-glucose- or galactose-containing media","volume":"49","author":"Swiss","year":"2011","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.tiv.2015.02.011","article-title":"The utility of HepG2 cells to identify direct mitochondrial dysfunction in the absence of cell death","volume":"29","author":"Kamalian","year":"2015","journal-title":"Toxicol. In Vitro"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/978-1-4939-7831-1_4","article-title":"High-Throughput Analysis of Mitochondrial Oxygen Consumption","volume":"1782","author":"Hynes","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s10863-012-9446-z","article-title":"Assessment of drug-induced mitochondrial dysfunction via altered cellular respiration and acidification measured in a 96-well platform","volume":"44","author":"Nadanaciva","year":"2012","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.taap.2007.06.003","article-title":"Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration","volume":"223","author":"Nadanaciva","year":"2007","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1093\/toxsci\/kfn056","article-title":"In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone","volume":"103","author":"Dykens","year":"2008","journal-title":"Toxicol. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.taap.2008.08.013","article-title":"Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro","volume":"233","author":"Dykens","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.taap.2013.06.019","article-title":"Toxicity assessments of nonsteroidal anti-inflammatory drugs in isolated mitochondria, rat hepatocytes, and zebrafish show good concordance across chemical classes","volume":"272","author":"Nadanaciva","year":"2013","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1177\/1087057110373547","article-title":"High-content screening for compounds that affect mtDNA-encoded protein levels in eukaryotic cells","volume":"15","author":"Nadanaciva","year":"2010","journal-title":"J. Biomol. Screen."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1006\/taap.1994.1246","article-title":"Disruption of mitochondrial calcium homeostasis following chronic doxorubicin administration","volume":"129","author":"Solem","year":"1994","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0005-2728(97)00055-8","article-title":"Preferential oxidation of cardiac mitochondrial DNA following acute intoxication with doxorubicin","volume":"1321","author":"Palmeira","year":"1997","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1034\/j.1600-0773.2003.930301.x","article-title":"Doxorubicin-induced cardiac mitochondrionopathy","volume":"93","author":"Wallace","year":"2003","journal-title":"Pharmacol. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s00280-009-0932-x","article-title":"Doxorubicin-induced mitochondrial dysfunction is secondary to nuclear p53 activation in H9c2 cardiomyoblasts","volume":"64","author":"Sardao","year":"2009","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1001\/jamainternmed.2015.8581","article-title":"Changes in Prescription and Over-the-Counter Medication and Dietary Supplement Use among Older Adults in the United States, 2005 vs 2011","volume":"176","author":"Qato","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/jhm.2614","article-title":"Medications associated with geriatric syndromes and their prevalence in older hospitalized adults discharged to skilled nursing facilities","volume":"11","author":"Saraf","year":"2016","journal-title":"J. Hosp. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1111\/jgs.14870","article-title":"Common Drug Side Effects and Drug-Drug Interactions in Elderly Adults in Primary Care","volume":"65","author":"Merel","year":"2017","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_65","first-page":"499","article-title":"Influence of anti-inflammatory agents on rat liver mitochondrial ATPase","volume":"26","author":"Chatterjee","year":"1976","journal-title":"Arzneimittel-Forschung"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1097\/00005344-200411000-00012","article-title":"Inhibition of cardiac mitochondrial respiration by salicylic acid and acetylsalicylate","volume":"44","author":"Szweda","year":"2004","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Raza, H., and John, A. (2012). Implications of altered glutathione metabolism in aspirin-induced oxidative stress and mitochondrial dysfunction in HepG2 cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036325"},{"key":"ref_68","first-page":"894","article-title":"Inhibition by salicylic acid of the activation and thus oxidation of long chain fatty acids. Possible role in the development of Reye\u2019s syndrome","volume":"259","author":"Deschamps","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1093\/toxsci\/kfg045","article-title":"Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition","volume":"73","author":"Oh","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1001\/archinte.1981.00340030065013","article-title":"Effects of aspirin and acetaminophen on the liver","volume":"141","author":"Zimmerman","year":"1981","journal-title":"Arch. Intern. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s00204-014-1378-4","article-title":"Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo","volume":"90","author":"Bonifacio","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"53","DOI":"10.14712\/fb2016062020053","article-title":"Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration","volume":"62","author":"Fisar","year":"2016","journal-title":"Folia Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ejphar.2017.09.031","article-title":"Validation of a pharmacological model for mitochondrial dysfunction in healthy subjects using simvastatin: A randomized placebo-controlled proof-of-pharmacology study","volume":"815","author":"Berends","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/cbin.10949","article-title":"Facilitation of Ca(2+) -induced opening of the mitochondrial permeability transition pore either by nicotinamide nucleotide transhydrogenase deficiency or statins treatment","volume":"42","author":"Busanello","year":"2018","journal-title":"Cell Biol. Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1016\/j.bbrc.2005.10.108","article-title":"Simvastatin induces impairment in skeletal muscle while heart is protected","volume":"338","author":"Sirvent","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.bbrc.2005.02.070","article-title":"Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle","volume":"329","author":"Sirvent","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/nbt1387","article-title":"Large-scale chemical dissection of mitochondrial function","volume":"26","author":"Wagner","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"396","DOI":"10.2174\/138955751505150408142032","article-title":"Mitochondrial carnitine\/acylcarnitine translocase: Insights in structure\/function relationships. Basis for drug therapy and side effects prediction","volume":"15","author":"Tonazzi","year":"2015","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"11863","DOI":"10.1038\/s41598-017-11070-x","article-title":"Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat beta-Cells. Direct Effect of Oxidative Stress","volume":"7","author":"Urbano","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1096\/fj.201800876R","article-title":"Atorvastatin, but not pravastatin, inhibits cardiac Akt\/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes","volume":"33","author":"Godoy","year":"2019","journal-title":"FASEB J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.abb.2017.12.003","article-title":"Atorvastatin affects negatively respiratory function of isolated endothelial mitochondria","volume":"637","author":"Broniarek","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1081\/DMR-200033494","article-title":"Acetaminophen-induced hepatotoxicity: Role of metabolic activation, reactive oxygen\/nitrogen species, and mitochondrial permeability transition","volume":"36","author":"Hinson","year":"2004","journal-title":"Drug Metab. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jhep.2004.09.015","article-title":"Involvement of mitochondrial permeability transition in acetaminophen-induced liver injury in mice","volume":"42","author":"Masubuchi","year":"2005","journal-title":"J. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00204-015-1537-2","article-title":"Real-time monitoring of oxygen uptake in hepatic bioreactor shows CYP450-independent mitochondrial toxicity of acetaminophen and amiodarone","volume":"90","author":"Prill","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"453","DOI":"10.3389\/fphar.2018.00453","article-title":"Mitochondrial-Lysosomal Axis in Acetaminophen Hepatotoxicity","volume":"9","author":"Moles","year":"2018","journal-title":"Front. Pharmacol."},{"key":"ref_86","first-page":"209","article-title":"Effects of ethacrynic acid and furosemide on isolated rat kidney mitochondria: Inhibition of electron transport in the region of phosphorylation site II","volume":"198","author":"Manuel","year":"1976","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_87","first-page":"1446","article-title":"Effect of furosemide on mitochondrial electron transport system and oxidative phosphorylation","volume":"33","author":"Orita","year":"1983","journal-title":"Arzneimittel-Forschung"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0378-4274(00)00218-6","article-title":"The role of mitochondrial injury in bromobenzene and furosemide induced hepatotoxicity","volume":"116","author":"Wong","year":"2000","journal-title":"Toxicol. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijcard.2007.10.022","article-title":"High dose clopidogrel decreases mice liver mitochondrial respiration function in vitro","volume":"133","author":"Tai","year":"2009","journal-title":"Int. J. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tox.2013.03.002","article-title":"Toxicity of thienopyridines on human neutrophil granulocytes and lymphocytes","volume":"308","author":"Maseneni","year":"2013","journal-title":"Toxicology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.freeradbiomed.2013.06.007","article-title":"Hepatocellular toxicity of clopidogrel: Mechanisms and risk factors","volume":"65","author":"Zahno","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.etp.2016.11.006","article-title":"Carvedilol exacerbate gentamicin-induced kidney mitochondrial alterations in adult rat","volume":"69","author":"Felix","year":"2017","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3389\/fphar.2017.00185","article-title":"Pravastatin Chronic Treatment Sensitizes Hypercholesterolemic Mice Muscle to Mitochondrial Permeability Transition: Protection by Creatine or Coenzyme Q10","volume":"8","author":"Busanello","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1177\/0192623307311412","article-title":"Rosuvastatin: Characterization of induced myopathy in the rat","volume":"36","author":"Westwood","year":"2008","journal-title":"Toxicol. Pathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.tiv.2011.11.013","article-title":"Differential involvement of mitochondrial dysfunction, cytochrome P450 activity, and active transport in the toxicity of structurally related NSAIDs","volume":"26","author":"Unlu","year":"2012","journal-title":"Toxicol. In Vitro"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/S0006-2952(98)00330-X","article-title":"Inhibition and uncoupling of oxidative phosphorylation by nonsteroidal anti-inflammatory drugs: Study in mitochondria, submitochondrial particles, cells, and whole heart","volume":"57","author":"Bravo","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1093\/toxsci\/KFS197","article-title":"Prediction of liver injury induced by chemicals in human with a multiparametric assay on isolated mouse liver mitochondria","volume":"129","author":"Porceddu","year":"2012","journal-title":"Toxicol. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1002\/hep.27206","article-title":"Human drug-induced liver injury severity is highly associated with dual inhibition of liver mitochondrial function and bile salt export pump","volume":"60","author":"Aleo","year":"2014","journal-title":"Hepatology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3138\/ptc.2012-65","article-title":"Statin-induced rhabdomyolysis: A comprehensive review of case reports","volume":"66","author":"Mendes","year":"2014","journal-title":"Physiother. Can."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s11883-010-0120-9","article-title":"Evidence-based management of statin myopathy","volume":"12","author":"Harper","year":"2010","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2165\/00002018-200528080-00002","article-title":"The effect of HMG-CoA reductase inhibitors on coenzyme Q10: Possible biochemical\/clinical implications","volume":"28","author":"Hargreaves","year":"2005","journal-title":"Drug Saf."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.clpt.2005.03.006","article-title":"High-dose statins and skeletal muscle metabolism in humans: A randomized, controlled trial","volume":"78","author":"Paiva","year":"2005","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jpeds.2010.08.015","article-title":"Rosuvastatin lowers coenzyme Q10 levels, but not mitochondrial adenosine triphosphate synthesis, in children with familial hypercholesterolemia","volume":"158","author":"Avis","year":"2011","journal-title":"J. Pediatr."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Will, Y., and Dykens, J. (2018). Statin and Fibrate-induced Dichotomy of Mitochondrial Function. Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants, Wiley.","DOI":"10.1002\/9781119329725"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40264-016-0417-x","article-title":"Drug-Induced Mitochondrial Toxicity","volume":"39","author":"Hargreaves","year":"2016","journal-title":"Drug Saf."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.taap.2005.03.004","article-title":"Statins and PPARalpha agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment","volume":"208","author":"Johnson","year":"2005","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3109\/00498254.2015.1046975","article-title":"Toxicity of macrolide antibiotics on isolated heart mitochondria: A justification for their cardiotoxic adverse effect","volume":"46","author":"Salimi","year":"2016","journal-title":"Xenobiotica"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1128\/AAC.49.8.3251-3255.2005","article-title":"Mitochondrial ribosome as the target for the macrolide antibiotic clarithromycin in the helminth Echinococcus multilocularis","volume":"49","author":"Mathis","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2131\/jts.42.267","article-title":"Joint toxicity of fluoroquinolone and tetracycline antibiotics to zebrafish (Danio rerio) based on biochemical biomarkers and histopathological observation","volume":"42","author":"Ding","year":"2017","journal-title":"J. Toxicol. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"54","DOI":"10.12788\/jcso.0167","article-title":"Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: A collaborative investigation by scientists and members of a social network","volume":"14","author":"Kaur","year":"2016","journal-title":"J. Community Support. Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1517\/17425255.2015.973401","article-title":"Mitochondrial toxicity of cardiac drugs and its relevance to mitochondrial disorders","volume":"11","author":"Finsterer","year":"2015","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2017.11.019","article-title":"Mitochondrial dysfunction in obesity","volume":"192","author":"Costa","year":"2018","journal-title":"Life Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.2337\/db18-0417","article-title":"High-Fat Diet Causes Mitochondrial Dysfunction as a Result of Impaired ADP Sensitivity","volume":"67","author":"Miotto","year":"2018","journal-title":"Diabetes"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Jorgensen, W., Rud, K.A., Mortensen, O.H., Frandsen, L., Grunnet, N., and Quistorff, B. (2017). Your mitochondria are what you eat: A high-fat or a high-sucrose diet eliminates metabolic flexibility in isolated mitochondria from rat skeletal muscle. Physiol. Rep., 5.","DOI":"10.14814\/phy2.13207"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1080\/17461391.2013.823466","article-title":"Physical inactivity and muscle oxidative capacity in humans","volume":"14","author":"Gram","year":"2014","journal-title":"Eur. J. Sport Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"3165396","DOI":"10.1155\/2017\/3165396","article-title":"Impact of Aging and Exercise on Mitochondrial Quality Control in Skeletal Muscle","volume":"2017","author":"Kim","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e000469","DOI":"10.1136\/openhrt-2016-000469","article-title":"Added sugars drive nutrient and energy deficit in obesity: A new paradigm","volume":"3","author":"DiNicolantonio","year":"2016","journal-title":"Open Heart"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.physbeh.2017.09.024","article-title":"Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior","volume":"182","author":"Chen","year":"2017","journal-title":"Physiol. Behav."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"247","DOI":"10.2741\/4307","article-title":"Protective action of green tea catechins in neuronal mitochondria during aging","volume":"20","author":"Assuncao","year":"2015","journal-title":"Front. Biosci."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Lim, S., Ahn, S.Y., Song, I.C., Chung, M.H., Jang, H.C., Park, K.S., Lee, K.U., Pak, Y.K., and Lee, H.K. (2009). Chronic exposure to the herbicide, atrazine, causes mitochondrial dysfunction and insulin resistance. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005186"},{"key":"ref_121","first-page":"5","article-title":"Potential compounds for the treatment of mitochondrial disease","volume":"116","author":"Rai","year":"2015","journal-title":"Br. Med. Bull."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/8\/2\/32\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:51:08Z","timestamp":1760187068000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/8\/2\/32"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,11]]},"references-count":121,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["biology8020032"],"URL":"https:\/\/doi.org\/10.3390\/biology8020032","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,11]]}}}