{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:30:12Z","timestamp":1792074612309,"version":"4.4.0"},"reference-count":181,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Owerko Center at the Alberta Children\u2019s Hospital Research Institute"},{"id":[{"id":"https:\/\/ror.org\/00gmyvv50","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Mitochondrial dysfunction has been increasingly implicated in the pathobiology of neurodevelopmental conditions, particularly autism and attention-deficit\/hyperactivity disorder (ADHD). Because the developing brain is critically dependent on sustained ATP production, impairments in oxidative phosphorylation, mitochondrial dynamics, and redox balance may disrupt neuronal maturation, synaptic development, and neural circuit refinement during sensitive developmental periods. This review examines evidence from postmortem neurochemistry, genomics, magnetic resonance spectroscopy, and biomarker research to characterize mitochondrial impairment across autism and ADHD. Studies in autism report an elevated burden of heteroplasmic mitochondrial DNA (mtDNA) variants, along with alterations in mtDNA copy number, respiratory chain capacity, fission\u2013fusion dynamics, and antioxidant defenses. Postmortem data demonstrate reduced activity of electron transport chain Complexes I, III, and V in the frontal cortex, temporal lobe, and cerebellum. These bioenergetic abnormalities are accompanied by elevated oxidative stress markers alongside mitochondria-mediated immune activation. In vivo neuroimaging corroborates these findings through elevated cerebral lactate and reduced phosphocreatine-to-ATP ratios. Evidence in ADHD is limited, but similarly implicates mitochondrial dysfunction, consistent with the frequent co-occurrence of these conditions and their partially shared architecture. The available literature supports mitochondrial dysfunction as a transdiagnostic biological feature of neurodevelopmental conditions, with relevance to mechanistic biomarker identification and targeted therapeutic development.<\/jats:p>","DOI":"10.3390\/antiox15060764","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:59:38Z","timestamp":1781773178000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mitochondrial Dysfunction in Autism and Attention-Deficit\/Hyperactivity Disorder: Evidence from Genetic, Biochemical, and Neuroimaging Approaches"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6598-1152","authenticated-orcid":false,"given":"Tina R.","family":"Ram","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9405-5907","authenticated-orcid":false,"given":"Chunlong","family":"Mu","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Department of Microbiology, Immunology, and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-5650","authenticated-orcid":false,"given":"Sarah J.","family":"MacEachern","sequence":"additional","affiliation":[{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1224-979X","authenticated-orcid":false,"given":"Jane","family":"Shearer","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Cumming School of Medicine, Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"},{"name":"Hotchkiss Brain Institute, University of Calgary, Calgary, AB T2N 4N1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s41073-019-0064-8","article-title":"SANRA\u2014A Scale for the Quality Assessment of Narrative Review Articles","volume":"4","author":"Baethge","year":"2019","journal-title":"Res. 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