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Increasing evidence suggests that mitochondrial metabolism contributes to tumor aggressiveness; however, the molecular mechanisms regulating mitochondrial function in meningiomas remain poorly defined. Here, we investigated the role of mitochondrial transcription factor A (TFAM)\u2013driven mitochondrial biogenesis and translation in meningioma progression. We performed integrative transcriptomic, immunohistochemical, and mitochondrial DNA analyses in a well\u2010characterized cohort of 91 meningiomas, comprising World Health Organization grade 1 (G1) and grade 2 (G2) tumors with long\u2010term clinical follow\u2010up. RNA sequencing identified enrichment for mitochondrial metabolic pathways, including oxidative phosphorylation and ATP metabolism, that was preferentially activated in G2 meningiomas. TFAM and its upstream regulator PGC1\u03b1 were significantly upregulated at both mRNA and protein levels in G2 tumors and exhibited a positive correlation, consistent with enhanced mitochondrial biogenesis. Although mitochondrial DNA copy number did not differ significantly between grades, G2 meningiomas showed a trend toward increased mitochondrial mass. Notably, G2 meningiomas demonstrated marked enrichment of mitoribosomal genes, including\n                    <jats:italic>MRPL15<\/jats:italic>\n                    ,\n                    <jats:italic>MRPL35<\/jats:italic>\n                    ,\n                    <jats:italic>MRPL42<\/jats:italic>\n                    and\n                    <jats:italic>MRPS22<\/jats:italic>\n                    , whose expression correlated positively with\n                    <jats:italic>TFAM<\/jats:italic>\n                    and\n                    <jats:italic>PGC1\u03b1<\/jats:italic>\n                    expression levels. Network analysis identified TFAM as a central hub linking mitochondrial biogenesis, translation, and metabolic pathway activation. These findings were independently validated using a publicly available meningioma transcriptomic dataset. Together, our results reveal a TFAM\u2010centered mitochondrial regulatory program that integrates mitochondrial biogenesis, translational capacity, and oxidative metabolism in higher\u2010grade meningiomas. This mitochondrial translational axis represents a previously unrecognized mechanism underlying meningioma progression and highlights potential metabolic vulnerabilities for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70277","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T10:46:31Z","timestamp":1786617991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of a TFAM\u2010Dependent Mitochondrial Translational Axis Drives Oxidative Metabolism in Grade 2 Meningiomas"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2449-3773","authenticated-orcid":false,"given":"Stella G.","family":"Cavalcante","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology (LIM15), Department of Neurology, Faculdade de Medicina FMUSP Universidade de S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedito Jamilson Ara\u00fajo","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology (LIM15), Department of Neurology, Faculdade de Medicina FMUSP Universidade de S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-6432","authenticated-orcid":false,"given":"Antonio M.","family":"Lerario","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes University of Michigan Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-1436","authenticated-orcid":false,"given":"Paula R.","family":"Sola","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology (LIM15), Department of Neurology, Faculdade de Medicina FMUSP Universidade de S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-5973","authenticated-orcid":false,"given":"Sueli M.","family":"Oba\u2010Shinjo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology (LIM15), Department of Neurology, Faculdade de Medicina FMUSP Universidade de S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4419-7928","authenticated-orcid":false,"given":"Suely K. N.","family":"Marie","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biology (LIM15), Department of Neurology, Faculdade de Medicina FMUSP Universidade de S\u00e3o Paulo S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy131"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1807-59322011001300005"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.12.006"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.02.011"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02119-3"},{"issue":"5","key":"e_1_2_11_10_1","first-page":"354","article-title":"Clinical and Molecular Aspects of Diseases of Mitochondrial DNA Instability","volume":"32","author":"Mao C. 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