{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:10:56Z","timestamp":1790809856382,"version":"4.1.0"},"reference-count":65,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T00:00:00Z","timestamp":1729555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005191","name":"Craig H. Neilsen Foundation","doi-asserted-by":"publisher","award":["385450"],"award-info":[{"award-number":["385450"]}],"id":[{"id":"10.13039\/100005191","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rick Hansen Foundation","award":["385450"],"award-info":[{"award-number":["385450"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Spinal cord injury (SCI) pathology and pathophysiology can be attributed to both primary physical injury and secondary injury cascades. Secondary injury cascades involve dysregulated metabolism and energetic deficits directly linked to compromised mitochondrial bioenergetics. Rescuing mitochondrial function and reducing oxidative stress are associated with neuroprotection. In this regard, ketosis after traumatic brain injury (TBI), or after SCI, improves secondary neuropathology by decreasing oxidative stress, increasing antioxidants, reducing inflammation, and improving mitochondrial bioenergetics. Here, we follow up on our previous study and have used an exogenous ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE), as an alternative to a ketogenic diet, focusing on mitochondrial function between 1 and 14 days after injury. Starting 3 h following a cervical level 5 (C5) hemi-contusion injury, animals were fed either a standard control diet (SD) or a ketone ester diet (KED) combined with KE administered orally (OKE). We found that mitochondrial function was reduced after SCI at all times post-SCI, accompanied by reduced expression of most of the components of the electron transport chain (ETC). The KE rescued some of the bioenergetic parameters 1 day after SCI when D-\u03b2-Hydroxybutyrate (BHB) concentrations were ~2 mM. Still, most of the beneficial effects were observed 14 days after injury, with BHB concentrations reaching values of 4\u20136 mM. To our knowledge, this is the first report to show the beneficial effects of KE in rescuing mitochondrial function after SCI and demonstrates the suitability of KE in ameliorating the metabolic dysregulation that occurs after traumatic SCI without requiring a restrictive dietary regime.<\/jats:p>","DOI":"10.3390\/cells13211746","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T04:10:14Z","timestamp":1729570214000},"page":"1746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ketone Esters Partially and Selectively Rescue Mitochondrial Bioenergetics After Acute Cervical Spinal Cord Injury in Rats: A Time-Course"],"prefix":"10.3390","volume":"13","author":[{"given":"Oscar","family":"Seira","sequence":"first","affiliation":[{"name":"International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HyoJoon (David)","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Poovathukaran","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3237-7553","authenticated-orcid":false,"given":"Kieran","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Oxford, Oxford OX1 2JD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Boushel","sequence":"additional","affiliation":[{"name":"School of Kinesiology, University of British Columbia, Vancouver, BC V6T 1Z1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-1676","authenticated-orcid":false,"given":"Wolfram","family":"Tetzlaff","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, BC V5Z 1M9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alizadeh, A., Dyck, S.M., and Karimi-Abdolrezaee, S. (2019). Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00282"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100826","DOI":"10.1016\/j.mam.2019.10.003","article-title":"Neurological disorders and mitochondria","volume":"71","author":"Kowaltowski","year":"2020","journal-title":"Mol. Asp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41536-020-00107-x","article-title":"Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation","volume":"5","author":"Norat","year":"2020","journal-title":"NPJ Regen. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113332","DOI":"10.1016\/j.expneurol.2020.113332","article-title":"Mitochondria focused neurotherapeutics for spinal cord injury","volume":"330","author":"Rabchevsky","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.mito.2022.11.001","article-title":"Delivery of mitoceuticals or respiratory competent mitochondria to sites of neurotrauma","volume":"68","author":"Patel","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.mito.2023.01.009","article-title":"The role of mitochondrial energy metabolism in neuroprotection and axonal regeneration after spinal cord injury","volume":"69","author":"Cheng","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00018-022-04261-x","article-title":"Mitochondrial function in spinal cord injury and regeneration","volume":"79","author":"Slater","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s13311-011-0031-7","article-title":"Targeting mitochondrial function for the treatment of acute spinal cord injury","volume":"8","author":"McEwen","year":"2011","journal-title":"Neurotherapeutics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1002\/alz.12845","article-title":"Nutritional metabolism and cerebral bioenergetics in Alzheimer\u2019s disease and related dementias","volume":"19","author":"Yassine","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1017\/S0954422421000214","article-title":"Ketogenic diets and the nervous system: A scoping review of neurological outcomes from nutritional ketosis in animal studies","volume":"35","author":"Field","year":"2022","journal-title":"Nutr. Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104908","DOI":"10.1016\/j.neuint.2020.104908","article-title":"Therapeutic potential of nutraceuticals to protect brain after stroke","volume":"142","author":"Chelluboina","year":"2021","journal-title":"Neurochem. Int."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Carneiro, L., and Pellerin, L. (2021). Nutritional Impact on Metabolic Homeostasis and Brain Health. Front. Neurosci., 15.","DOI":"10.3389\/fnins.2021.767405"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.copbio.2020.12.009","article-title":"Ketogenic regimens for acute neurotraumatic events","volume":"70","author":"Li","year":"2021","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1080\/1028415X.2020.1853414","article-title":"The ketone ester, 3-hydroxybutyl-3-hydroxybutyrate, attenuates neurobehavioral deficits and im-proves neuropathology following controlled cortical impact in male rats","volume":"25","author":"Namboodiri","year":"2022","journal-title":"Nutr. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Seira, O., Kolehmainen, K., Liu, J., Streijger, F., Haegert, A., Lebihan, S., Boushel, R., and Tetzlaff, W. (2021). Ketogenesis controls mitochondrial gene expression and rescues mitochondrial bioenergetics after cervical spinal cord injury in rats. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-96003-5"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11064-020-03156-2","article-title":"Ketone Metabolite beta-Hydroxybutyrate Ameliorates Inflammation after Spinal Cord Injury by Inhibiting the NLRP3 Inflammasome","volume":"46","author":"Kong","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gough, S.M., Casella, A., Ortega, K.J., and Hackam, A.S. (2021). Neuroprotection by the Ketogenic Diet: Evidence and Controversies. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.782657"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1912","DOI":"10.4103\/1673-5374.280327","article-title":"Neuroprotective effects of a ketogenic diet in combination with exogenous ketone salts following acute spinal cord injury","volume":"15","author":"Tan","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106454","DOI":"10.1016\/j.eplepsyres.2020.106454","article-title":"Ketogenic diet and Neuroinflammation","volume":"167","author":"Koh","year":"2020","journal-title":"Epilepsy Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.yrtph.2012.04.008","article-title":"Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects","volume":"63","author":"Clarke","year":"2012","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-nutr-071816-064916","article-title":"beta-Hydroxybutyrate: A Signaling Metabolite","volume":"37","author":"Newman","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1042\/BST20190240","article-title":"Why a d-beta-hydroxybutyrate monoester?","volume":"48","author":"Norwitz","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104506","DOI":"10.1016\/j.yrtph.2019.104506","article-title":"Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults","volume":"109","author":"Vansant","year":"2019","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Streijger, F., Tigchelaar, S., Maloon, M., Liu, J., Tetzlaff, W., and Kwon, B.K. (2012). A contusive model of unilateral cervical spinal cord injury using the infinite horizon impactor. J. Vis. Exp., 3313.","DOI":"10.3791\/3313-v"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.neurobiolaging.2012.11.023","article-title":"A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer\u2019s disease","volume":"34","author":"Kashiwaya","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Mooren, F.C. (2012). Mitochondrial Respiration. Encyclopedia of Exercise Medicine in Health and Disease, Springer.","DOI":"10.1007\/978-3-540-29807-6"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1089\/neu.2006.0242","article-title":"Temporal characterization of mitochondrial bioenergetics after spinal cord injury","volume":"24","author":"Sullivan","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1089\/08977150152693692","article-title":"Traumatic brain injury-induced changes in gene expression and functional activity of mitochondrial cyto-chrome C oxidase","volume":"18","author":"Harris","year":"2001","journal-title":"J. Neurotrauma"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0197-0186(00)00102-9","article-title":"Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain","volume":"38","author":"Leino","year":"2001","journal-title":"Neurochem. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1016\/j.bbamcr.2016.03.013","article-title":"Monocarboxylate transporters in the brain and in cancer","volume":"1863","author":"Sboarina","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1471-4159.2005.03168.x","article-title":"Monocarboxylate transporters in the central nervous system: Distribution, regulation and function","volume":"94","author":"Pierre","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1139\/h05-002","article-title":"Distribution of monocarboxylate transporters MCT1-MCT8 in rat tissues and human skeletal muscle","volume":"31","author":"Bonen","year":"2006","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0014-5793(00)01889-5","article-title":"Lactate transport in rat adipocytes: Identification of monocarboxylate transporter 1 (MCT1) and its modulation during streptozotocin-induced diabetes","volume":"479","author":"Hajduch","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1113\/jphysiol.2007.138594","article-title":"Enhanced expression of three monocarboxylate transporter isoforms in the brain of obese mice","volume":"583","author":"Pierre","year":"2007","journal-title":"J. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Streijger, F., Plunet, W.T., Lee, J.H.T., Liu, J., Lam, C.K., Park, S., Hilton, B.J., Fransen, B.L., Matheson, K.A.J., and Assinck, P. (2013). Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078765"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.mito.2022.12.004","article-title":"beta-Hydroxybutyrate preferentially enhances neuron over astrocyte respiration while signaling cellular quiescence","volume":"68","author":"Koppel","year":"2023","journal-title":"Mitochondrion"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Van der Goot, M.H., Kooij, M., Stolte, S., Baars, A., Arndt, S.S., and van Lith, H.A. (2021). Incorporating inter-individual variability in experimental design improves the quality of results of animal experiments. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255521"},{"key":"ref_39","unstructured":"Dhillon, K.K., and Gupta, S. (2024, June 07). Biochemistry, Ketogenesis, StatPearls, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK493179\/."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1038\/ncomms4944","article-title":"The beta-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages","volume":"5","author":"Rahman","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1093\/abbs\/gmab079","article-title":"Acetoacetate promotes muscle cell proliferation via the miR-133b\/SRF axis through the Mek-Erk-MEF2 pathway","volume":"53","author":"Zhong","year":"2021","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1074\/jbc.M115.676510","article-title":"Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice","volume":"291","author":"Zou","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.toxlet.2020.01.015","article-title":"Acetoacetate enhances oxidative metabolism and response to toxicants of cultured kidney cells","volume":"323","author":"Denoon","year":"2020","journal-title":"Toxicol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"R829","DOI":"10.1152\/ajpregu.00506.2012","article-title":"Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats","volume":"304","author":"Pilla","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.nbd.2016.08.002","article-title":"Ketone ester supplementation attenuates seizure activity, and improves behavior and hippocampal synaptic plasticity in an Angelman syndrome mouse model","volume":"96","author":"Ciarlone","year":"2016","journal-title":"Neurobiol. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1089\/neu.1996.13.473","article-title":"Evaluation of a carbohydrate-free diet for patients with severe head injury","volume":"13","author":"Ritter","year":"1996","journal-title":"J. Neurotrauma"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1042\/BJ20141018","article-title":"High glucose induces mitochondrial dysfunction independently of protein O-GlcNAcylation","volume":"467","author":"Dassanayaka","year":"2015","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Fiorello, M.L., Treweeke, A.T., Macfarlane, D.P., and Megson, I.L. (2020). The impact of glucose exposure on bioenergetics and function in a cultured endothelial cell model and the implications for cardiovascular health in diabetes. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-76505-4"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Lam, C.H.-I., Cheung, J.K.-W., Tse, D.Y.-Y., and Lam, T.C. (2022). Proteomic Profiling Revealed Mitochondrial Dysfunction in Photoreceptor Cells under Hyperglycemia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232113366"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1738","DOI":"10.1096\/fj.01-1027com","article-title":"High glucose-induced oxidative stress and mitochondrial dysfunction in neurons","volume":"16","author":"Russell","year":"2002","journal-title":"FASEB J."},{"key":"ref_51","first-page":"100029","article-title":"Impact of ketogenic diet and ketone diester supplementation on body weight, blood glucose, and ketones in Sprague Dawley rats fed over two weeks","volume":"3","author":"Modica","year":"2021","journal-title":"Food Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41580-022-00506-6","article-title":"Mechanisms of mitochondrial respiratory adaptation","volume":"23","author":"Bennett","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41580-018-0092-0","article-title":"Mitochondrial proteins: From biogenesis to functional networks","volume":"20","author":"Pfanner","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xing, G., Barry, E.S., Benford, B., Grunberg, N.E., Li, H., Watson, W.D., and Sharma, P. (2013). Impact of repeated stress on traumatic brain injury-induced mitochondrial electron transport chain expression and behavioral responses in rats. Front. Neurol., 4.","DOI":"10.3389\/fneur.2013.00196"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.jtcvs.2009.08.060","article-title":"Electron transport chain dysfunction in neonatal pressure-overload hypertrophy precedes cardiomyocyte apoptosis independent of oxidative stress","volume":"139","author":"Griffiths","year":"2010","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"H54","DOI":"10.1152\/ajpheart.00699.2015","article-title":"Selective downregulation of mitochondrial electron transport chain activity and increased oxidative stress in human atrial fibrillation","volume":"311","author":"Emelyanova","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.1113\/JP270250","article-title":"Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training","volume":"593","author":"Montero","year":"2015","journal-title":"J. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1152\/japplphysiol.01081.2012","article-title":"Mitochondria express enhanced quality as well as quantity in association with aerobic fitness across recreationally active individuals up to elite athletes","volume":"114","author":"Jacobs","year":"2013","journal-title":"J. Appl. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/s41467-017-02694-8","article-title":"Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species","volume":"9","author":"Topf","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11250","DOI":"10.1523\/JNEUROSCI.0907-12.2012","article-title":"Post-translational oxidative modification and inactivation of mitochondrial complex I in epileptogenesis","volume":"32","author":"Ryan","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Alexeyev, M., Shokolenko, I., Wilson, G., and LeDoux, S. (2013). The maintenance of mitochondrial dna integrity--critical analysis and update. Cold Spring Harb. Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a012641"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E168","DOI":"10.1152\/ajpendo.00227.2018","article-title":"Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity","volume":"316","author":"Ngo","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nesci, S., Trombetti, F., Pagliarani, A., Ventrella, V., Algieri, C., Tioli, G., and Lenaz, G. (2021). Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology. Life, 11.","DOI":"10.3390\/life11030242"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1126\/science.1230381","article-title":"Supercomplex Assembly Determines Electron Flux in the Mitochondrial Electron Transport Chain","volume":"340","author":"Balsa","year":"2013","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.plefa.2003.09.007","article-title":"The therapeutic implications of ketone bodies: The effects of ketone bodies in pathological conditions: Ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism","volume":"70","author":"Veech","year":"2004","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/21\/1746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:17:52Z","timestamp":1760113072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/13\/21\/1746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,22]]},"references-count":65,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["cells13211746"],"URL":"https:\/\/doi.org\/10.3390\/cells13211746","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,22]]}}}