ArticleMolecular neurobiology2026
Distinct Mitochondrial Central Dogma Gene Expression in the Buffalo Brain: A Comparative Transcriptomic Study with Metabolically Active Organs.
Article in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
In long-lived neurons, precise control of mitochondrial gene expression is critical for maintaining bioenergetic capacity and preventing dysfunction linked to neurodegeneration. This control is executed by nuclear-encoded mitochondrial central dogma (NEM-CD) genes, yet their tissue-specific regulation, particularly in large mammalian brains, remains poorly defined. We conducted a comparative transcriptomic analysis of 214 NEM-CD genes across four buffalo tissues (brain/cerebellum, heart, kidney, and ovary) to elucidate organ-specific regulatory strategies. RNA sequencing and differential expression analysis revealed a definitive quantitative hierarchy (kidney > heart > brain > ovary), with tissue identity explaining 46.36% of intra-species transcriptomic variance (PC1). While the heart and kidney upregulated structural oxidative phosphorylation (OXPHOS) and translational machinery to meet high-throughput demands, the brain uniquely enriched genes governing transcriptional elongation (e.g., TEFM), RNA surveillance (e.g., PNPT1), and DNA repair (OGG1, POLG). Crucially, these findings were anchored by targeted LC-MS/MS proteomic screening, identifying brain-exclusive mitochondrial specialists such as SFXN3 and SLC25A14 (UCP5). Intra-species analysis revealed that the buffalo neuronal program participates in a robust body-wide regulatory plan (systemic coherence; median ρ = 0.8027), a synchronized architecture also observed in humans (median ρ = 0.9264). Subsequent cross-species compression identified a core set of highly conserved mitochondrial regulatory genes (e.g., ANGEL2, AARS2, RECQL4, MTFMT) that maintain strict evolutionary stability between humans and buffalo. Collectively, this study identifies a conserved "Precision-over-Throughput" neuroprotective strategy in mammalian brains, prioritizing transcriptional fidelity and genome maintenance over biogenic volume. This shared regulatory framework provides a stable comparative foundation for understanding mitochondrial dysregulation in both humans and large farm animals, offering a high-fidelity roadmap for neurodegenerative research.
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