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overproduction of superoxide anions, with reactive oxygen species (ROS) generally being considered the link between high glucose levels and the toxicity seen at cellular levels. Respiratory complex anomalies can lead to the production of ROS. Calcium [Ca2+] at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production, which can be lethal to the mitochondria through various mechanisms. F1F0-ATPase (ATP synthase or complex V) is the enzyme responsible for catalyzing the final step of oxidative phosphorylation. This is achieved by F1F0-ATPase coupling the translocation of protons in the mitochondrial intermembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space, thereby blocking ATP synthesis and, in turn, leading to Neuropathy, Ataxia, and Retinitis Pigmentosa (NARP) syndrome. This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain-mediated mitochondrial stress. NARP cybrids are the in vitro experimental models of cells with F1FO-ATPase defects, with these cells harboring 98% of mtDNA T8993G mutations. Their counterparts, 143B osteosarcoma cell lines, are the parental cell lines used for comparison. We observed that NARP cells mediated and enhanced the death of cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose, as depicted using the MTT assay of cell viability. Furthermore, using fluorescence probe-coupled laser scanning confocal imaging microscopy, NARP cells were found to significantly enable mitochondrial reactive oxygen species (mROS) formation and enhance the depolarization of the mitochondrial membrane potential (\u0394\u03a8m). Elucidating the mechanisms of sugar-enhanced toxicity on the mitochondria may, in the future, help to alleviate the symptoms of patients with NARP syndromes and other neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/biology13080639","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T03:32:01Z","timestamp":1724643121000},"page":"639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathological Role of High Sugar in Mitochondrial Respiratory Chain Defect-Augmented Mitochondrial Stress"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3997-9260","authenticated-orcid":false,"given":"Ebrima D.","family":"Cham","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wenhua 1st Road, Kweishan, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-I","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Chang Gung Memorial Hospital, Keelung Branch, Keelung 204, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Jie","family":"Jou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wenhua 1st Road, Kweishan, Taoyuan 333, Taiwan"},{"name":"Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S110","DOI":"10.2337\/diabetes.53.2007.S110","article-title":"Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes","volume":"53","author":"Green","year":"2004","journal-title":"Diabetes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R283","DOI":"10.1093\/hmg\/ddi270","article-title":"Emerging functions of mammalian mitochondrial fusion and fission","volume":"14","author":"Chen","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0140-6736(04)17665-4","article-title":"Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients","volume":"365","author":"Vanhorebeek","year":"2005","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kemppainen, E., George, J., Garipler, G., Tuomela, T., Kiviranta, E., Soga, T., Dunn, C.D., and Jacobs, H.T. (2016). Correction: Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151421"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tins.2020.10.004","article-title":"Mitochondria and Calcium in Alzheimer\u2019s Disease: From Cell Signaling to Neuronal Cell Death","volume":"44","author":"Bacskai","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/jpp\/rgae011","article-title":"Chrysin bonded to beta-d-glucose tetraacetate enhances its protective effects against the neurotoxicity induced by aluminum in Swiss mice","volume":"76","author":"Okoh","year":"2024","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0163-7827(00)00005-9","article-title":"The biosynthesis and functional role of cardiolipin","volume":"39","author":"Schlame","year":"2000","journal-title":"Prog. Lipid Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6591","DOI":"10.1093\/emboj\/20.23.6591","article-title":"Specific roles of protein-phospholipid interactions in the yeast cytochrome bc1 complex structure","volume":"20","author":"Lange","year":"2001","journal-title":"EMBO J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1042\/bj3640317","article-title":"Cardiolipin prevents rate-dependent uncoupling and provides osmotic stability in yeast mitochondria","volume":"364","author":"Koshkin","year":"2002","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1073\/pnas.241655498","article-title":"Cytochrome c release from mitochondria proceeds by a two-step process","volume":"99","author":"Ott","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"52873","DOI":"10.1074\/jbc.M308366200","article-title":"Cardiolipin stabilizes respiratory chain supercomplexes","volume":"278","author":"Pfeiffer","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1056\/NEJMra022567","article-title":"Mitochondrial respiratory-chain diseases","volume":"348","author":"DiMauro","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1089\/ars.2010.3284","article-title":"High-glucose stimulation increases reactive oxygen species production through the calcium and mitogen-activated protein kinase-mediated activation of mitochondrial fission","volume":"14","author":"Yu","year":"2011","journal-title":"Antioxid. Redox Signal"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4177","DOI":"10.1074\/jbc.275.6.4177","article-title":"Catalytic activities of mitochondrial ATP synthase in patients with mitochondrial DNA T8993G mutation in the ATPase 6 gene encoding subunit a","volume":"275","author":"Baracca","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/978-3-319-55330-6_32","article-title":"Mitochondria-Targeted Antioxidants for the Treatment of Cardiovascular Disorders","volume":"982","author":"Kim","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.2337\/db07-1781","article-title":"Mitochondrial networking protects beta-cells from nutrient-induced apoptosis","volume":"58","author":"Molina","year":"2009","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/S0006-3495(98)77920-2","article-title":"Imaging the permeability pore transition in single mitochondria","volume":"74","author":"Huser","year":"1998","journal-title":"Biophys. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/hmg\/ddp503","article-title":"Mitochondrial DNA background modifies the bioenergetics of NARP\/MILS ATP6 mutant cells","volume":"19","author":"Davidson","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1212\/WNL.56.5.687","article-title":"The T9176G mtDNA mutation severely affects ATP production and results in Leigh syndrome","volume":"56","author":"Carrozzo","year":"2001","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1136\/jmg.2003.012047","article-title":"Respiratory chain complex V deficiency due to a mutation in the assembly gene ATP12","volume":"41","author":"Seneca","year":"2004","journal-title":"J. Med. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.3748\/wjg.15.4137","article-title":"Problems associated with glucose toxicity: Role of hyperglycemia-induced oxidative stress","volume":"15","author":"Kawahito","year":"2009","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1126\/science.1219855","article-title":"Mitochondrial fission, fusion, and stress","volume":"337","author":"Youle","year":"2012","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.tem.2021.01.006","article-title":"Cardiolipin, Mitochondria, and Neurological Disease","volume":"32","author":"Falabella","year":"2021","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"749","DOI":"10.4103\/1673-5374.249218","article-title":"Mitophagy links oxidative stress conditions and neurodegenerative diseases","volume":"14","author":"Shefa","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bhansali, S., Bhansali, A., Walia, R., Saikia, U.N., and Dhawan, V. (2017). Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with Prediabetes and Type 2 Diabetes Mellitus. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2017.00347"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e12538","DOI":"10.1111\/jpi.12538","article-title":"Protective stabilization of mitochondrial permeability transition and mitochondrial oxidation during mitochondrial Ca2+ stress by melatonin\u2019s cascade metabolites C3-OHM and AFMK in RBA1 astrocytes","volume":"66","author":"Jou","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1600-079X.2007.00490.x","article-title":"Melatonin protects against common deletion of mitochondrial DNA-augmented mitochondrial oxidative stress and apoptosis","volume":"43","author":"Jou","year":"2007","journal-title":"J. Pineal Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tem.2012.11.003","article-title":"Neuroinflammation and neurodegeneration in overnutrition-induced diseases","volume":"24","author":"Cai","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Huang, W.Y., Jou, M.J., and Peng, T.I. (2013). mtDNA T8993G mutation-induced F1F0-ATP synthase defect augments mitochondrial dysfunction associated with hypoxia\/reoxygenation: The protective role of melatonin. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0081546"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"H258","DOI":"10.1152\/ajpheart.00348.2003","article-title":"Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: Role of cardiolipin","volume":"287","author":"Lesnefsky","year":"2004","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S0891-5849(99)00032-5","article-title":"Lipid peroxidation and alterations to oxidative metabolism in mitochondria isolated from rat heart subjected to ischemia and reperfusion","volume":"27","author":"Paradies","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1096\/fj.02-0729fje","article-title":"Decreased complex III activity in mitochondria isolated from rat heart subjected to ischemia and reperfusion: Role of reactive oxygen species and cardiolipin","volume":"17","author":"Petrosillo","year":"2003","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrm3696","article-title":"The autophagosome: Origins unknown, biogenesis complex","volume":"14","author":"Lamb","year":"2013","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6311","DOI":"10.1016\/j.febslet.2006.10.036","article-title":"Interaction of peroxidized cardiolipin with rat-heart mitochondrial membranes: Induction of permeability transition and cytochrome c release","volume":"580","author":"Petrosillo","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/j.freeradbiomed.2009.06.032","article-title":"Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release","volume":"47","author":"Petrosillo","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/S0167-7799(97)01068-8","article-title":"Selective targeting of bioactive compounds to mitochondria","volume":"15","author":"Murphy","year":"1997","journal-title":"Trends Biotechnol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0169-409X(99)00069-1","article-title":"Drug delivery to mitochondria: The key to mitochondrial medicine","volume":"41","author":"Murphy","year":"2000","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.arr.2018.08.003","article-title":"Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence","volume":"47","author":"Park","year":"2018","journal-title":"Ageing Res. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1146\/annurev.pharmtox.47.120505.105110","article-title":"Targeting antioxidants to mitochondria by conjugation to lipophilic cations","volume":"47","author":"Murphy","year":"2007","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e12698","DOI":"10.1016\/j.heliyon.2022.e12698","article-title":"The role of dietary antioxidants in type 2 diabetes and neurodegenerative disorders: An assessment of the benefit profile","volume":"9","author":"Fatima","year":"2023","journal-title":"Heliyon"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Tuell, D.S., Los, E.A., Ford, G.A., and Stone, W.L. (2023). The Role of Natural Antioxidant Products That Optimize Redox Status in the Prevention and Management of Type 2 Diabetes. 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