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Vol.:(0123456789)Amino Acids (2025) 57:17 https://doi.org/10.1007/s00726-025-03447-4ORIGINAL ARTICLEUnveiling the tissue?specif i c landscape of nuclear?encoded mitochondrial genes involved in amino acid  metabolism in buf f aloE. M. Sadeesh 1  · Madhuri S. Lahamge 1 Received: 16 October 2024 / Accepted: 16 February 2025 / Published online: 28 February 2025 © The Author(s) 2025AbstractMitochondria play a pivotal role in energy production, metabolism, and cellular signaling, serving as key regulators of cel-lular functions, including dif f erentiation and tissue-specif i c adaptation. The interplay between mitochondria and the nucleus is crucial for coordinating these processes, particularly through the supply of metabolites for epigenetic modif i cations that facilitate nuclear-mitochondrial interactions. To investigate tissue-specif i c mitochondrial adaptations at the molecular level, we conducted RNA sequencing data analyses of kidney, heart, brain, and ovary tissues of female buf f aloes, focusing on variations in mitochondrial gene expression related to amino acid metabolism. Our analysis identif i ed 82 nuclear-encoded mitochondrial transcripts involved in amino acid metabolism, with signif i cant dif f erential expression patterns across all tissues. Notably, the heart, brain, and kidney—tissues with higher energy demands—exhibited elevated expression levels compared to the ovary. The kidney displayed unique gene expression patterns, characterized by up-regulation of genes involved in glyoxylate metabolism and amino acid catabolism. In contrast, comparative analysis of the heart and kidney versus the brain revealed shared up-regulation of genes associated with fatty acid oxidation. Gene ontology and KEGG pathway analyses conf i rmed the enrichment of genes in pathways related to amino acid degradation and metabolism. These fi ndings highlight the tissue-specif i c regulation of mitochondrial gene expression linked to amino acid metabolism, ref l ect-ing mitochondrial adaptations to the distinct metabolic and energy requirements of dif f erent tissues in buf f alo. Importantly, our results underscore the relevance of mitochondrial adaptations not only for livestock health but also for understanding metabolic disorders in humans. By elucidating the molecular mechanisms of mitochondrial function and their tissue-specif i c variations, this study provides insights that could inform breeding strategies for enhanced livestock productivity and contrib-ute to therapeutic approaches for human metabolic diseases. Thus, our fi ndings illustrate how mitochondria are specialized in a tissue-specif i c manner to optimize amino acid utilization and maintain cellular homeostasis, with implications for both animal welfare and human health.Keywords Mitochondria · Nuclear · Buf f alo · Amino acid · Tissue-specif i cIntroductionOxidative phosphorylation (OXPHOS) is the major hub for cellular bioenergetics, signaling, and metabolism medi-ated by mitochondria. The response mechanism to oxygen uptake of almost all cells is the OXPHOS, consisting of fi ve enzyme complexes and two electron carriers that generate ATP (Javadov et al. 2020; Vercellino and Sazanov 2022). Although mitochondria are highly dynamic organelles, they also have their own DNA (mtDNA), which in collaboration with mitochondrial biogenesis plays a crucial role in the syn-chronized process of mtDNA replication, transcription, and translation. Mitochondrial tricarboxylic acid (TCA) cycle and OXPHOS, are essentials for the metabolism of energy Handling editor: S. Gross. * E. M. Sadeesh sadeeshcirb@gmail.com Madhuri S. Lahamge madhurilahamgevet@gmail.com1 Laboratory of Mitochondrial Biology of Farm Animals, Animal Biochemistry Division, ICAR-National Dairy Research Institute, Karnal, Haryana 132001, India