Unveiling the tissue-specific landscape of nuclear-encoded mitochondrial genes involved in amino acid metabolism in buffalo

Abstract

Mitochondria play a pivotal role in energy production, metabolism, and cellular signaling, serving as key regulators of cellular functions, including differentiation and tissue-specific adaptation. The interplay between mitochondria and the nucleus is crucial for coordinating these processes, particularly through the supply of metabolites for epigenetic modifications that facilitate nuclear-mitochondrial interactions. To investigate tissue-specific mitochondrial adaptations at the molecular level, we conducted RNA sequencing data analyses of kidney, heart, brain, and ovary tissues of female buffaloes, focusing on variations in mitochondrial gene expression related to amino acid metabolism. Our analysis identified 82 nuclear-encoded mitochondrial transcripts involved in amino acid metabolism, with significant differential 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 confirmed the enrichment of genes in pathways related to amino acid degradation and metabolism. These findings highlight the tissue-specific regulation of mitochondrial gene expression linked to amino acid metabolism, reflecting mitochondrial adaptations to the distinct metabolic and energy requirements of different tissues in buffalo. 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-specific variations, this study provides insights that could inform breeding strategies for enhanced livestock productivity and contribute to therapeutic approaches for human metabolic diseases. Thus, our findings illustrate how mitochondria are specialized in a tissue-specific manner to optimize amino acid utilization and maintain cellular homeostasis, with implications for both animal welfare and human health.

Keywords: Amino acid; Buffalo; Mitochondria; Nuclear; Tissue-specific.

Fig. 1

Heatmap of hierarchical clustering of gene expression based on normalized count across tissues—kidney, heart, brain, and ovary. Colour key indicates the level of expression. The variability in gene expression between tissues is represented by the height of the dendrogram branches

Fig. 2

Differential gene expression analysis across various tissue comparisons (kidney versus heart, kidney versus brain, kidney versus ovary, heart versus brain, heart versus ovary, brain versus ovary). a Histogram of DEG number statistics b A Circular heatmap illustrating a hierarchical cluster analysis of Gene expression. The color key indicates expression levels. The scale on the right-hand side shows the color code relative to log₂ fold-change (log₂-FC) in gene abundance. The variability in gene expression between tissues is reflected in the height of the dendrogram branches

Fig. 3

The volcano plot of differentially expressed genes was plotted across various tissue comparison a kidney versus heart b kidney versus brain c kidney versus ovary d heart versus brain e heart versus ovary f brain versus ovary. The x-axis is the log2 expression values (fold change), and the y-axis values are the base mean expression values (Adj p-value)

Fig. 4

Functional enrichment analysis results of differentially expressed genes across various comparisons: a kidney versus heart b kidney versus brain c kidney versus ovary d heart versus brain e heart versus ovary f brain versus ovary. The enrichment network cneplot shows the link between key DEGs and significant enriched BP. Each cluster ID is indicated with a specific colour. GO Gene ontology, DEGs differentially expressed genes, BP biological processes, CC cellular components, MF molecular functions

Fig. 5

The KEGG pathway enrichment analysis of DEGs. The significantly shared KEGG pathways of DEGs between different tissue comparison groups via KEGG enrichment analysis. a Kidney versus heart b kidney versus brain c kidney versus ovary d heart versus brain e heart versus ovary f brain versus ovary