Distinct Mitochondrial Central Dogma Gene Expression in the Buffalo Brain: A Comparative Transcriptomic Study with...

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.