Mito-Nuclear Interactions in Livestock: Implications for Adaptation, Productivity, and Precision Breeding.

Mitochondria are central regulators of cellular energy metabolism, stress responses, and physiological adaptation, with their functions depending on the coordinated interaction between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). These mito-nuclear interactions are essential for maintaining oxidative phosphorylation (OXPHOS), cellular homeostasis, and overall organismal fitness. Increasing evidence suggests that mito-nuclear compatibility influences a wide range of economically important traits in livestock, including growth, milk production, reproduction, feed efficiency, disease resistance, and environmental adaptation. This review provides a comprehensive overview of mitochondrial and nuclear genome organization, mechanisms of mito-nuclear communication, and their biological significance in livestock species. Key mechanisms discussed include mito-nuclear co-evolution, anterograde and retrograde signaling, reactive oxygen species (ROS)-mediated signaling, epigenetic regulation, mitophagy, mitochondrial biogenesis, and mito-nuclear incompatibility. The review further highlights the role of mito-nuclear interactions in adaptation to heat stress, high-altitude environments, metabolic challenges, and disease resistance, as well as their influence on productivity traits such as milk yield, growth performance, fertility, reproductive efficiency, and longevity. Advances in genomic and multi-omics technologies, including genome-wide association studies (GWAS), mitogenomics, transcriptomics, proteomics, metabolomics, single-cell omics, network biology, and systems genomics, have greatly enhanced our understanding of mitochondrial function and its contribution to complex traits. Furthermore, integrating mitochondrial information into genomic selection, marker-assisted breeding, climate-smart livestock improvement, and precision livestock farming (PLF) offers new opportunities to enhance productivity, resilience, and sustainability. Understanding the genetic and functional basis of mito-nuclear interactions will facilitate the development of next-generation precision breeding strategies aimed at improving livestock performance under changing environmental conditions.