Metabolic Plasticity and Transcriptomic Reprogramming Orchestrate Hypoxia Adaptation in Yak.

Area of Science:

• Physiology
• Molecular Biology
• High-altitude Adaptation

Background:

• Yaks (Bos grunniens) possess exceptional resilience to hypoxia.
• Understanding yak adaptation mechanisms is crucial for studying high-altitude survival.

Purpose of the Study:

• To investigate the impact of oxygen concentration on yak cardiac fibroblast proliferation.
• To elucidate the molecular regulatory pathways involved in yak hypoxia adaptation.

Main Methods:

• RNA sequencing (RNA-seq) for gene expression analysis.
• Live-cell metabolic assessment to evaluate cellular respiration and glycolysis.
• Bioinformatic analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction networks.

Main Results:

• Hypoxia significantly inhibited cardiac fibroblast proliferation and activity.
• Mitochondrial DNA (mtDNA) content remained stable, but mtDNA-encoded oxidative phosphorylation components were upregulated.
• Metabolic analyses showed mitochondrial respiratory inhibition and enhanced glycolysis under hypoxia.
• RNA-seq identified key hypoxia adaptation genes like HK2, TPI1, and HIF-1α, involved in metabolic regulation.
• Consensus hub genes (CCNA2, PLK1, TP53) were identified as potentially involved in hypoxia adaptation.

Conclusions:

• Yak adaptation to hypoxia involves significant metabolic reprogramming.
• Enhanced glycolysis and coordinated upregulation of oxidative phosphorylation components are key survival mechanisms.
• This study provides molecular insights into high-altitude adaptation in yaks.