{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:58:54Z","timestamp":1790607534523,"version":"4.1.0"},"reference-count":120,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403075"],"award-info":[{"award-number":["82403075"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gliomas are metabolically heterogeneous tumors in which mitochondria coordinate bioenergetics, biosynthesis, redox homeostasis, stress adaptation, and treatment responses. This review examines mitochondrial dependencies across glioma subtypes and cell states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We synthesized evidence on mitochondrial integration of glucose, amino acid and protein, lipid, and nucleotide metabolism, together with mitochondrial genetics, signaling, intercellular transfer, and barriers to therapeutic translation in gliomas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Glioma glucose metabolism does not follow a uniform Warburg phenotype. IDH\u2010mutant gliomas exhibit D\u20102\u2010hydroxyglutarate\u2010driven metabolic and epigenetic remodeling, whereas IDH\u2010wild\u2010type glioblastomas contain glycolytic, oxidative phosphorylation\u2010enriched, and adaptable stem\u2010like states. Mitochondrial proteostasis links protein import and translation with PI3K\/AKT\/mTOR signaling, the ubiquitin\u2013proteasome system, autophagy, and mitophagy. Lipid synthesis, storage, fatty acid oxidation, and cardiolipin homeostasis support metabolic adaptation. Electron transport, aspartate availability, redox balance, and dihydroorotate dehydrogenase connect mitochondria with nucleotide synthesis, DNA repair, and treatment resistance. Mitochondrial DNA alterations, mitonuclear signaling, and intercellular mitochondrial transfer further influence respiratory adaptation and tumorigenicity. Metabolic compensation and intratumoral heterogeneity limit single\u2010target therapies, whereas clinical evidence supports genotype\u2010directed intervention, exemplified by vorasidenib.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Effective mitochondrial targeting requires biomarkers that match metabolic dependencies to molecular subtypes and cell states while accounting for brain exposure, compensation, and toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71180","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T14:30:13Z","timestamp":1790605813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Metabolic Reprogramming in Glioma: Mechanisms of Tumorigenesis and Implications for Clinical Therapy"],"prefix":"10.1002","volume":"32","author":[{"given":"Liangqi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Clinical Research Center for Skull Base Surgery and Neurooncology in Hunan Province  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Clinical Research Center for Skull Base Surgery and Neurooncology in Hunan Province  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Clinical Research Center for Skull Base Surgery and Neurooncology in Hunan Province  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1357-4866","authenticated-orcid":false,"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Clinical Research Center for Skull Base Surgery and Neurooncology in Hunan Province  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6675-2481","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Clinical Research Center for Skull Base Surgery and Neurooncology in Hunan Province  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"3","key":"e_1_2_18_2_1","first-page":"165","article-title":"Primary Brain and Other Central Nervous System Tumors in the United States (2014\u20102018): A Summary of the CBTRUS Statistical Report for Clinicians","volume":"9","author":"Low J. 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