{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:08:20Z","timestamp":1788797300679,"version":"build-2803163510"},"reference-count":138,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>Sleep is an essential biological function with unclear mechanisms. Recent research links the circadian clock, energy metabolism, calcium handling, reactive oxygen species (ROS) production, and synaptic plasticity to cognitive performance. Given that mitochondria regulate cellular energy production, calcium buffering, and ROS dynamics, it stands to reason that mitochondrial function plays a significant role in sleep regulation. Here, we propose an enhanced integrative framework \u201cthe mitochondrial theory of sleep\u201d that synthesizes disease models, mechanistic details, and gene enrichment analysis based on bioinformatics. We identified nine crucial mitochondrial protein-coding genes that are highly enriched in pathways linked to oxidative phosphorylation, synaptic processes, and sleep characteristics by closely analyzing data sets using Gene Ontology, KEGG, and Reactome databases. Our analysis suggests that sleep deprivation is associated with calcium signaling, mitochondrial genes expression, reactive oxygen species (ROS) generation, and ATP production. Additionally, coherent mitochondrial genes cluster linked to neuroprotective and sleep-inducing effects are revealed by functional clustering and network topology analysis. This study offers a testable model for the control of wakefulness and sleep by the mitochondria. This mechanistic model incorporates findings from research on humans and animals, psychiatric conditions including bipolar disorder, and evolutionary theories. This framework identifies promising therapeutic targets for future investigation, including (MCU1, CPT1A, and antioxidant regulators) to treat sleep disorders in addition to bringing disparate findings together from a biological perspectives. While much of the current evidence remains correlative, this framework provides a roadmap for future studies. By highlighting the function of mitochondrial dynamics as an integrating point for metabolic and neurophysiological mechanisms of sleep, our findings advance our theoretical and practical understanding of sleep.<\/jats:p>","DOI":"10.3389\/fpsyt.2026.1922556","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:14:51Z","timestamp":1788794091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The mitochondrial theory of sleep: an integrative framework for understanding sleep-wake regulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Seithikurippu R.","family":"Pandi-Perumal","sequence":"first","affiliation":[{"name":"Central Research Facility (CRF), Dr D.Y Patil Medical College Hospital and Research Centre, Dr D.Y Patil Vidyapeeth","place":["Pune, India"]},{"name":"Centre for Research and Development, Chandigarh University","place":["Mohali, Punjab, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Molecular Biology, The University of Texas Medical Branch at Galveston","place":["Galveston, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konda Mani","family":"Saravanan","sequence":"additional","affiliation":[{"name":"Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University","place":["Rajpura, Punjab, India"]},{"name":"Center for Innovation and Inclusive Research, Sharda University","place":["Greater Noida, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arehally M.","family":"Mahalakshmi","sequence":"additional","affiliation":[{"name":"Centre for Experimental Pharmacology & Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]},{"name":"Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saravana Babu","family":"Chidambaram","sequence":"additional","affiliation":[{"name":"Centre for Experimental Pharmacology & Toxicology, Central Animal Facility, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]},{"name":"Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education & Research","place":["Mysuru, Karnataka, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ganesh Pandian","family":"Namasivayam","sequence":"additional","affiliation":[{"name":"Institute for Integrated Cell-Material Sciences (WPI-iCeMS), A210, Kyoto University Institute for Advanced Study","place":["Kyoto, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2697","article-title":"Sleep viewed as a state of adaptive inactivity","volume":"10","author":"Siegel","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/0166-4328(95)00002-B","article-title":"Energy conservation and sleep","volume":"69","author":"Berger","year":"1995","journal-title":"Behav Brain Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(94)00057-O","article-title":"Restoration of brain energy metabolism as the function of sleep","volume":"45","author":"Benington","year":"1995","journal-title":"Prog Neurobiol"},{"key":"B4","article-title":"Sleep as a restorative process: Human clues","volume-title":"Progress in Brain Research","author":"Oswald","year":"1980"},{"key":"B5","first-page":"289","article-title":"Sleep as a restorative process and a theory to explain why","volume-title":"Progress in Brain Research","author":"Adam","year":"1980"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-011-1044-0","article-title":"Sleep and immune function","volume":"463","author":"Besedovsky","year":"2012","journal-title":"Pfl\u00fcgers Arch - Eur J Physiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.cophys.2019.11.008","article-title":"Sleep and thermoregulation","volume":"15","author":"Harding","year":"2020","journal-title":"Curr Opin Physiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2741\/1054","article-title":"Thermoregulation and sleep","volume":"1","author":"Parmeggiani","year":"2003","journal-title":"Front Biosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-7634(05)80208-8","article-title":"A brain-warming function for REM sleep","volume":"16","author":"Wehr","year":"1992","journal-title":"Neurosci Biobehav Rev"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1016\/B978-0-12-813743-7.00027-X","article-title":"Chapter 27 - Sleep and brain development","volume-title":"Handbook of Sleep Research","author":"Shaffery","year":"2019"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0166-4328(95)00018-O","article-title":"A functional role for REM sleep in brain maturation","volume":"69","author":"Marks","year":"1995","journal-title":"Behav Brain Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2869.1993.tb00088.x","article-title":"The importance of REM sleep for brain maturation","volume":"2","author":"Mirmiran","year":"1993","journal-title":"J Sleep Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuron.2013.12.025","article-title":"Sleep and the price of plasticity: From synaptic and cellular homeostasis to memory consolidation and integration","volume":"81","author":"Tononi","year":"2014","journal-title":"Neuron"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241224","article-title":"Sleep drives metabolite clearance from the adult brain","volume":"342","author":"Xie","year":"2013","journal-title":"Science (80-)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2697","article-title":"Sleep - Opinion sleep viewed as a state of adaptive inactivity","volume":"10","author":"Siegel","year":"2009","journal-title":"Nat Rev Neurosci"},{"key":"B16","first-page":"3","article-title":"The function(s) of sleep","volume-title":"Sleep-Wake Neurobiology and Pharmacology","author":"Frank","year":"2019"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3934\/Neuroscience.2015.3.155","article-title":"The functions of sleep","volume":"2","author":"Assefa","year":"2015","journal-title":"AIMS Neurosci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature04285","article-title":"Clues to the functions of mammalian sleep","volume":"437","author":"Siegel","year":"2005","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1353\/pbm.1998.0051","article-title":"Current perspectives on the function of sleep","volume":"41","author":"Rechtschaffen","year":"2015","journal-title":"Perspect Biol Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0165-1781(98)00089-4","article-title":"Role of REM sleep and dream affect in overnight mood regulation: a study of normal volunteers","volume":"81","author":"Cartwright","year":"1998","journal-title":"Psychiatry Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.08.031","article-title":"Sleep-dependent learning and memory consolidation","volume":"44","author":"Walker","year":"2004","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3537-16.2017","article-title":"Targeted memory reactivation during sleep adaptively promotes the strengthening or weakening of overlapping memories","volume":"37","author":"Oyarz\u00fan","year":"2017","journal-title":"J Neurosci"},{"key":"B23","first-page":"1187170","article-title":"The effects of sleep and targeted memory reactivation on the consolidation of relevant and irrelevant information","volume-title":"Front Sleep","author":"Barner","year":"2023"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2023.08.003","article-title":"Sleep and memory consolidation in aging: A neuroimaging perspective","volume":"179","author":"Hamel","year":"2023","journal-title":"Rev Neurol (Paris)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202657119","article-title":"Sleep preferentially consolidates negative aspects of human memory: Well-powered evidence from two large online experiments","volume":"119","author":"Denis","year":"2022","journal-title":"Proc Natl Acad Sci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0269439","article-title":"Sleep bolsters schematically incongruent memories","volume":"17","author":"Ashton","year":"2022","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1152\/physrev.00032.2012","article-title":"About sleep\u2019s role in memory","volume":"93","author":"Rasch","year":"2013","journal-title":"Physiol Rev"},{"key":"B28","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1146\/annurev-clinpsy-032813-153716","article-title":"The role of sleep in emotional brain function","volume":"10","author":"Goldstein","year":"2014","journal-title":"Annu Rev Clin Psychol"},{"key":"B29","first-page":"1","article-title":"Cognitive neuroscience of sleep","volume-title":"Progress in Brain Research","author":"Poe","year":"2010"},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/j.1479-8425.2006.00254.x","article-title":"Information processing in sleep based on event-related activities of the brain","volume":"5","author":"Karaka\u015f","year":"2007","journal-title":"Sleep Biol Rhythms"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.crvi.2004.05.009","article-title":"Neural reapportionment: an hypothesis to account for the function of sleep","volume":"327","author":"Gally","year":"2004","journal-title":"CR Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.1846","article-title":"Sleep: A health imperative","volume":"35","author":"Luyster","year":"2012","journal-title":"Sleep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1080\/10673220802432517","article-title":"Sleep-dependent memory processing","volume":"16","author":"Walker","year":"2008","journal-title":"Harv Rev Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09261-y","article-title":"Mitochondrial origins of the pressure to sleep","volume":"645","author":"Sarnataro","year":"2025","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyg.2020.575328","article-title":"Phosphorylation hypothesis of sleep","volume":"11","author":"Ode","year":"2020","journal-title":"Front Psychol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neures.2017.03.012","article-title":"Ca2+-dependent hyperpolarization hypothesis for mammalian sleep","volume":"118","author":"Tatsuki","year":"2017","journal-title":"Neurosci Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.05.007","article-title":"Fast and slow Ca2+-dependent hyperpolarization mechanisms connect membrane potential and sleep homeostasis","volume":"44","author":"Ode","year":"2017","journal-title":"Curr Opin Neurobiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fnsys.2022.1059421","article-title":"The role of calcium and CaMKII in sleep","volume":"16","author":"Wang","year":"2022","journal-title":"Front Syst Neurosci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201700105","article-title":"Ca2+-dependent hyperpolarization pathways in sleep homeostasis and mental disorders","volume":"40","author":"Shi","year":"2018","journal-title":"BioEssays"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai8355","article-title":"Homer1a drives homeostatic scaling-down of excitatory synapses during sleep","volume":"355","author":"Diering","year":"2017","journal-title":"Science (80-)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12030674","article-title":"Mitochondria need their sleep: Redox, bioenergetics, and temperature regulation of circadian rhythms and the role of cysteine-mediated redox signaling, uncoupling proteins, and substrate cycles","volume":"12","author":"Richardson","year":"2023","journal-title":"Antioxidants"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1113\/JP288054","article-title":"Neurobiology of mitochondrial dynamics in sleep","volume":"603","author":"Sarnataro","year":"2025","journal-title":"J Physiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2026.106556","article-title":"FKBP51 mediates mitochondrial function via NF-\u03baB pathway during sleep fragmentation-induced cognitive impairment","volume":"136","author":"Ji","year":"2026","journal-title":"Brain Behav Immun"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.2147\/NSS.S518388","article-title":"Changed serum levels of Sirtuin1 and Sirtuin3 and their correlations with sleep quality and cognitive function in patients with chronic insomnia disorder","volume":"18","author":"Liu","year":"2026","journal-title":"Nat Sci Sleep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2026.101302","article-title":"Characterization of a UQCRC1 variant in a patient with progressive weakness, pain and sleep issues reveals a functional mitochondrial defect restored by mitochondrial transplantation","volume":"46","author":"Piroli","year":"2026","journal-title":"Mol Genet Metab Rep"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2026.121741","article-title":"Mitochondrial homeostasis regulation in the prefrontal cortex: A key mechanism for emodin-mediated attenuation of insomnia","volume":"367","author":"Zhang","year":"2026","journal-title":"J Ethnopharmacol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s12017-026-08917-w","article-title":"Miro1 in Parkinson\u2019s disease: A key regulator of mitochondrial homeostasis and neurodegeneration","volume":"28","author":"Singh","year":"2026","journal-title":"NeuroMolecular Med"},{"key":"B48","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1146\/annurev-cellbio-120420-015303","article-title":"Mitochondria as cellular and organismal signaling hubs","volume":"38","author":"Shen","year":"2022","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.24.13807","article-title":"Regulation of mitochondrial ATP synthesis by calcium: Evidence for a long-term metabolic priming","volume":"96","author":"Jouaville","year":"1999","journal-title":"Proc Natl Acad Sci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.pbiomolbio.2025.03.001","article-title":"Myelin: a possible proton capacitor for energy storage during sleep and energy supply during wakefulness","volume":"196","author":"Morelli","year":"2025","journal-title":"Prog Biophys Mol Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E21-12-0610-T","article-title":"Hierarchical integration of mitochondrial and nuclear positioning pathways by the Num1 EF hand","volume":"33","author":"Anderson","year":"2022","journal-title":"Mol Biol Cell"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1034-5","article-title":"A potassium channel \u03b2-subunit couples mitochondrial electron transport to sleep","volume":"568","author":"Kempf","year":"2019","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2023.102733","article-title":"Mitochondrial control of sleep","volume":"81","author":"Hartmann","year":"2023","journal-title":"Curr Opin Neurobiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/28.1.21","article-title":"Differences in activity of cytochrome C oxidase in brain between sleep and wakefulness","volume":"28","author":"Nikonova","year":"2005","journal-title":"Sleep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsac047","article-title":"Perspective \u2013 ultrastructural analyses reflect the effects of sleep and sleep loss on neuronal cell biology","volume":"45","author":"Wang","year":"2022","journal-title":"Sleep"},{"key":"B56","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.smrv.2014.07.003","article-title":"Oxidative stress in obstructive sleep apnea and intermittent hypoxia \u2013 revisited \u2013 the bad ugly and good: implications to the heart and brain","volume":"20","author":"Lavie","year":"2015","journal-title":"Sleep Med Rev"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2008.08.003","article-title":"The energy hypothesis of sleep revisited","volume":"86","author":"Scharf","year":"2008","journal-title":"Prog Neurobiol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181978","article-title":"Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status","volume":"12","author":"Trivedi","year":"2017","journal-title":"PloS One"},{"key":"B59","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00210-013-0955-z","article-title":"Differential effects of paradoxical sleep deprivation on memory and oxidative stress","volume":"387","author":"Lima","year":"2014","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12931-015-0205-7","article-title":"Mitochondrial DNA alteration in obstructive sleep apnea","volume":"16","author":"Lacedonia","year":"2015","journal-title":"Respir Res"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/0306-9877(94)90071-X","article-title":"The free radical flux theory of sleep","volume":"43","author":"Reimund","year":"1994","journal-title":"Med Hypotheses"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2005206","article-title":"A bidirectional relationship between sleep and oxidative stress in Drosophila","volume":"16","author":"Hill","year":"2018","journal-title":"PloS Biol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1016\/j.cell.2020.04.049","article-title":"Sleep loss can cause death through accumulation of reactive oxygen species in the gut","volume":"181","author":"Vaccaro","year":"2020","journal-title":"Cell"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12081600","article-title":"Sleep deprivation-induced oxidative stress in rat models: a scoping systematic review","volume":"12","author":"Neculicioiu","year":"2023","journal-title":"Antioxidants"},{"key":"B65","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.pnpbp.2012.01.018","article-title":"Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals","volume":"39","author":"de Souza","year":"2012","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2017.01.015","article-title":"Pathological consequences of MICU1 mutations on mitochondrial calcium signalling and bioenergetics","volume":"1864","author":"Bhosale","year":"2017","journal-title":"Biochim Biophys Acta Mol Cell Res"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4373","DOI":"10.1016\/j.cub.2020.08.052","article-title":"A role for astroglial calcium in mammalian sleep and sleep regulation","volume":"30","author":"Ingiosi","year":"2020","journal-title":"Curr Biol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.jare.2021.01.006","article-title":"Sleep\/wake calcium dynamics, respiratory function, and ROS production in cardiac mitochondria","volume":"31","author":"Abdel-Rahman","year":"2021","journal-title":"J Adv Res"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21987","article-title":"BCL-2 and BAX proteins expression throughout the light\u2013dark cycle and modifications induced by sleep deprivation and rebound in adult rat brain","volume":"87","author":"Montes-Rodr\u00edguez","year":"2009","journal-title":"J Neurosci Res"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2016.00025","article-title":"Rapid eye movement sleep deprivation induces neuronal apoptosis by noradrenaline acting on alpha1 adrenoceptor and by triggering mitochondrial intrinsic pathway","volume":"7","author":"Somarajan","year":"2016","journal-title":"Front Neurol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2016.10.037","article-title":"Neurobiological basis of bipolar disorder: mitochondrial dysfunction hypothesis and beyond","volume":"187","author":"Kato","year":"2017","journal-title":"Schizophr Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2000.020305.x","article-title":"Mitochondrial dysfunction in bipolar disorder","volume":"2","author":"Kato","year":"2000","journal-title":"Bipolar Disord"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2020.110299","article-title":"Mechanisms of insulin resistance, mitochondrial dysfunction and the action of the ketogenic diet in bipolar disorder. Focus on the PI3K\/AKT\/HIF1-a pathway","volume":"145","author":"Campbell","year":"2020","journal-title":"Med Hypotheses"},{"key":"B74","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.sleep.2023.11.011","article-title":"Association of sleep quality and mitochondrial DNA copy number in healthy middle-aged adults","volume":"113","author":"Han","year":"2024","journal-title":"Sleep Med"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2017.01.014","article-title":"A model of the mitochondrial basis of bipolar disorder","volume":"74","author":"Morris","year":"2017","journal-title":"Neurosci Biobehav Rev"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115652","article-title":"Mitochondrial dysfunction: a fatal blow in depression","volume":"167","author":"Song","year":"2023","journal-title":"BioMed Pharmacother"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-021-00116-w","article-title":"Identification of a novel MICU1 nonsense variant causes myopathy with extrapyramidal signs in an Iranian consanguineous family","volume":"8","author":"Bitarafan","year":"2021","journal-title":"Mol Cell Pediatr"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/326320","article-title":"Melatonin in mitochondrial dysfunction and related disorders","volume":"2011","author":"Srinivasan","year":"2011","journal-title":"Int J Alzheimer\u2019s Dis"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2105607","article-title":"Oxidative stress in neurodegenerative diseases: from a mitochondrial point of view","volume":"2019","author":"Cenini","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102374","article-title":"Role of mitochondrial DNA damage in ROS-mediated pathogenesis of age-related macular degeneration (AMD)","volume":"20","author":"Kaarniranta","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B81","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s11910-021-01121-2","article-title":"Sleep disorders in mitochondrial diseases","volume":"21","author":"Brunetti","year":"2021","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B82","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm Sin B"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102307","article-title":"The mechanisms of mitochondrial abnormalities that contribute to sleep disorders and related neurodegenerative diseases","volume":"97","author":"Zhang","year":"2024","journal-title":"Ageing Res Rev"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01498-7","article-title":"Increased interaction between endoplasmic reticulum and mitochondria following sleep deprivation","volume":"21","author":"Aboufares El Alaoui","year":"2023","journal-title":"BMC Biol"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1016\/j.cub.2023.03.008","article-title":"Chronic sleep loss sensitizes &lt;em&gt;Drosophila melanogaster&lt;\/em&gt; to nitrogen stress","volume":"33","author":"Bedont","year":"2023","journal-title":"Curr Biol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2013.10.015","article-title":"The endoplasmic reticulum\u2013mitochondria connection: one touch, multiple functions","volume":"1837","author":"Marchi","year":"2014","journal-title":"Biochim Biophys Acta Bioenerg"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3440","article-title":"Endoplasmic reticulum\u2013mitochondria contacts: function of the junction","volume":"13","author":"Rowland","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.bbalip.2013.11.014","article-title":"MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond","volume":"1841","author":"Vance","year":"2014","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5370.1763","article-title":"Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses","volume":"280","author":"Rizzuto","year":"1998","journal-title":"Science (80-)"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200608073","article-title":"Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels","volume":"175","author":"Szabadkai","year":"2006","journal-title":"J Cell Biol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/nature10230","article-title":"A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter","volume":"476","author":"De Stefani","year":"2011","journal-title":"Nature"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1021\/bi2018909","article-title":"Role of mitochondrial Ca 2+ in the regulation of cellular energetics","volume":"51","author":"Glancy","year":"2012","journal-title":"Biochemistry"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201700105","article-title":"Ca 2+ \u2010dependent hyperpolarization pathways in sleep homeostasis and mental disorders","volume":"40","author":"Shi","year":"2018","journal-title":"BioEssays"},{"key":"B94","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.tibs.2005.05.008","article-title":"Bridging gaps in phospholipid transport","volume":"30","author":"Voelker","year":"2005","journal-title":"Trends Biochem Sci"},{"key":"B95","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1083\/jcb.201006159","article-title":"Making heads or tails of phospholipids in mitochondria","volume":"192","author":"Osman","year":"2011","journal-title":"J Cell Biol"},{"key":"B96","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.plipres.2013.07.002","article-title":"Lipids of mitochondria","volume":"52","author":"Horvath","year":"2013","journal-title":"Prog Lipid Res"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbabio.2009.06.004","article-title":"SR\/ER\u2013mitochondrial local communication: calcium and ROS","volume":"1787","author":"Csord\u00e1s","year":"2009","journal-title":"Biochim Biophys Acta Bioenerg"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.040","article-title":"Redox nanodomains are induced by and control calcium signaling at the ER-mitochondrial interface","volume":"63","author":"Booth","year":"2016","journal-title":"Mol Cell"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/234952","article-title":"Sleep deprivation and oxidative stress in animal models: a systematic review","volume":"2015","author":"Villafuerte","year":"2015","journal-title":"Oxid Med Cell Longev"},{"key":"B100","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.neuron.2016.02.032","article-title":"Involvement of Ca(2+)-Dependent Hyperpolarization in Sleep Duration in Mammals","volume":"90","author":"Tatsuki","year":"2016"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/S0005-2728(98)00161-3","article-title":"The mitochondrial genome: structure, transcription, translation and replication","volume":"1410","author":"Taanman","year":"1999","journal-title":"Biochim Biophys Acta Bioenerg"},{"key":"B102","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/s0005-2728(98)00120-0","article-title":"Role of mitochondria in oxidative stress and ageing","volume":"1366","author":"Lenaz","year":"1998","journal-title":"Biochim Biophys Acta"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001824","article-title":"Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes","volume":"11","author":"Kasahara","year":"2006","journal-title":"Mol Psychiatry"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2022.11.010","article-title":"Association analyses of the autosomal genome and mitochondrial DNA with accelerometry-derived sleep parameters in depressed UK biobank subjects","volume":"157","author":"Melhuish Beaupre","year":"2023","journal-title":"J Psychiatr Res"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.5068","article-title":"Mitochondrial DNA copy number in sleep duration discordant monozygotic twins","volume":"38","author":"Wrede","year":"2015","journal-title":"Sleep"},{"key":"B106","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1093\/sleep\/33.7.889","article-title":"Changes in components of energy regulation in mouse cortex with increases in wakefulness","volume":"33","author":"Nikonova","year":"2010","journal-title":"Sleep"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.900947","article-title":"Liver X receptor gene expression is enhanced in children with obstructive sleep apnea-hyperpnoea syndrome and cyclooxygenase-2 (COX-2) is correlated with severity of obstructive sleep apnea-hypopnea syndrome (OSAHS)","volume":"23","author":"Ye","year":"2017","journal-title":"Med Sci Monit"},{"key":"B108","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.nbscr.2019.01.003","article-title":"Sleep and circadian defects in a Drosophila model of mitochondrial encephalomyopathy","volume":"6","author":"Fogle","year":"2019","journal-title":"Neurobiol Sleep Circadian Rhythm"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22116054","article-title":"Mitochondrial glucocorticoid receptors and their actions","volume":"22","author":"Kokkinopoulou","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1038\/s41437-022-00554-w","article-title":"Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster","volume":"129","author":"Anderson","year":"2022","journal-title":"Heredity (Edinb)"},{"key":"B111","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.cmet.2025.04.016","article-title":"Hydrogen peroxide in midbrain sleep neurons regulates sleep homeostasis","volume":"37","author":"Tian","year":"2025","journal-title":"Cell Metab"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.3389\/fragi.2025.1605070","article-title":"Unraveling the interplay between sleep, redox metabolism, and aging: Implications for brain health and longevity","volume":"6","author":"Mir","year":"2025","journal-title":"Front Aging"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2025.102667","article-title":"Oxidative stress and mitochondrial impairment: Key drivers in neurodegenerative disorders","volume":"104","author":"Wen","year":"2025","journal-title":"Ageing Res Rev"},{"key":"B114","doi-asserted-by":"publisher","first-page":"4","DOI":"10.3892\/etm.2020.9132","article-title":"The role of reactive oxygen species in cognitive impairment associated with sleep apnea","volume":"20","author":"Xu","year":"2020","journal-title":"Exp Ther Med"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2025.115153","article-title":"Sleep fragmentation impairs cognitive function and exacerbates Alzheimer\u2019s disease-related pathology in a mouse model by disrupting mitochondrial biogenesis","volume":"386","author":"Liu","year":"2025","journal-title":"Exp Neurol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.neuropharm.2003.11.032","article-title":"Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice","volume":"46","author":"Silva","year":"2004","journal-title":"Neuropharmacology"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.5664\/jcsm.4212","article-title":"Sleep disorders associated with primary mitochondrial diseases","volume":"10","author":"J.","year":"2025","journal-title":"J Clin Sleep Med"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1080\/19768354.2024.2347503","article-title":"Circadian coordination: Understanding interplay between circadian clock and mitochondria","volume":"28","author":"Kim","year":"2024","journal-title":"Anim Cells Syst (Seoul)"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101110","article-title":"Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms","volume":"43","author":"Saner","year":"2021","journal-title":"Mol Metab"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.143699","article-title":"Identification of mitochondrial energy metabolism genes associated with obstructive sleep apnea syndrome: Integrated bioinformatics analysis","volume":"311","author":"Jiang","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1056691","article-title":"Construction of a mitochondrial dysfunction related signature of diagnosed model to obstructive sleep apnea","volume":"13","author":"Liu","year":"2022","journal-title":"Front Genet"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2026.109071","article-title":"Mitochondrial dysfunction in patients with severe obstructive sleep apnea","volume":"146","author":"Huang","year":"2026","journal-title":"Sleep Med"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2026.102191","article-title":"Energy beats: Daily and circadian rhythms in mitochondrial biology","volume":"91","author":"Ceccato","year":"2026","journal-title":"Mitochondrion"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163500","article-title":"Quantitative proteomics of sleep-deprived mouse brains reveals global changes in mitochondrial proteins","volume":"11","author":"Ren","year":"2016","journal-title":"PloS One"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0306152","article-title":"Maternal total sleep deprivation causes oxidative stress and mitochondrial dysfunction in oocytes associated with fertility decline in mice","volume":"19","author":"Yi","year":"2024","journal-title":"PloS One"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5685-07.2008","article-title":"Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling","volume":"28","author":"Naidoo","year":"2008","journal-title":"J Neurosci"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2019.112760","article-title":"Sleep profile during fasting in PPAR-alpha knockout mice","volume":"214","author":"Kondo","year":"2020","journal-title":"Physiol Behav"},{"key":"B128","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s11910-018-0868-9","article-title":"Cerebral metabolic changes during sleep","volume":"18","author":"Aalling","year":"2018","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18020248","article-title":"The function of the mitochondrial calcium uniporter in neurodegenerative disorders","volume":"18","author":"Liao","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbscr.2023.100100","article-title":"The unified theory of sleep: Eukaryotes endosymbiotic relationship with mitochondria and REM the push-back response for awakening","volume":"15","author":"Adams","year":"2023","journal-title":"Neurobiol Sleep Circadian Rhythm"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17122124","article-title":"Melatonin: A mitochondrial targeting molecule involving mitochondrial protection and dynamics","volume":"17","author":"Tan","year":"2016","journal-title":"Int J Mol Sci"},{"key":"B132","first-page":"96","article-title":"Growth hormone and cortisol secretion in relation to sleep and wakefulness","volume":"16","author":"Davidson","year":"1991","journal-title":"J Psychiatry Neurosci"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-29-1-20","article-title":"Growth hormone secretion during nocturnal sleep in normal subjects1","volume":"29","author":"Honda","year":"1969","journal-title":"J Clin Endocrinol Metab"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.3390\/ctn8010006","article-title":"Cellular stress, energy constraints and the energy allocation hypothesis of sleep","volume":"8","author":"Schmidt","year":"2024","journal-title":"Clin Transl Neurosci"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2014.08.001","article-title":"The energy allocation function of sleep: A unifying theory of sleep, torpor, and continuous wakefulness","volume":"47","author":"Schmidt","year":"2014","journal-title":"Neurosci Biobehav Rev"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13070833","article-title":"Sleep deprivation triggers mitochondrial DNA release in microglia to induce neural inflammation: Preventative effect of hydroxytyrosol butyrate","volume":"13","author":"Hu","year":"2024","journal-title":"Antioxidants"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.3390\/molecules31091381","article-title":"Biochemical mechanisms of cellular stress adaptation in the pathogenesis of chronic diseases","volume":"31","author":"Lemanowicz","year":"2026","journal-title":"Molecules"},{"key":"B138","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1007\/s11011-026-01853-5","article-title":"Mitochondrial dysfunction in sleep deprivation","volume":"41","author":"Zhao","year":"2026","journal-title":"Metab Brain Dis"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1922556\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:14:54Z","timestamp":1788794094000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1922556\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":138,"alternative-id":["10.3389\/fpsyt.2026.1922556"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1922556","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1922556"}}