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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Mitochondria regulate cellular metabolism, signaling, and cell fate, yet the biological significance of coordinated mitochondrial genome transcription in lower-grade glioma (LGG) remains unclear. We integrated transcriptomic and clinical data from the TCGA and CGGA cohorts to investigate expression of the 13 mitochondrial DNA-encoded protein-coding genes (mtPCGs). Elevated expression of all mtPCGs was consistently associated with favorable molecular subtypes and prolonged overall survival (OS). Transcriptome-wide correlation and Gene Ontology analyses revealed a coordinated program enriched for synaptic signaling, neurotransmission, postsynaptic organization, and neuronal differentiation, accompanied by positive correlations with neuronal and synaptic markers and negative correlations with stemness and immune-associated markers. Although the mitochondrial transcriptional score was not independently associated with survival after adjustment for established clinicomolecular variables, it consistently marked biologically less aggressive tumors. Coordinated mitochondrial genome expression identifies a neuron-like transcriptional state associated with favorable LGG biology, revealing an unexpected link between mitochondrial transcription, synaptic identity, and glioma differentiation.<\/jats:p>","DOI":"10.3390\/ijms27167289","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"7289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Coordinated Mitochondrial Genome Expression Program Marks a Differentiated Neural-Lineage and Synaptic Transcriptional State in Lower-Grade Glioma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2604-6350","authenticated-orcid":false,"given":"Henrique Ritter","family":"Dal-Pizzol","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute for Basic Health Sciences, Federal University of 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Alegre 90620-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6435-6626","authenticated-orcid":false,"given":"Caroline Brunetto","family":"de Farias","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Children\u2019s Cancer Institute (ICI), Porto Alegre 90620-110, Brazil"},{"name":"Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7958-1279","authenticated-orcid":false,"given":"Andr\u00e9 T.","family":"Brunetto","sequence":"additional","affiliation":[{"name":"Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre 90035-003, Brazil"},{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Children\u2019s Cancer Institute (ICI), Porto Alegre 90620-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo R.","family":"Isolan","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Children\u2019s Cancer Biology and Pediatric Oncology\u2014INCT BioOncoPed, Porto Alegre 90035-003, Brazil"},{"name":"Graduate Program in Principles of Surgery, 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