Feedback regulation between AMPK and HIF-1α contributes to color stability via energy metabolism and mitochondrial efficiency regulation of yak meat

Abstract

Despite the well-established individual roles of AMP-activated protein kinase (AMPK) and hypoxia-inducible factor-1α (HIF-1α) in sensing energy stress and/or hypoxia in postmortem muscle, a knowledge gap persists regarding their interplay and the consequent impact on the yak meat color stability. This study aimed to elucidate the AMPK–HIF–1α interaction and its consequential impact on mitochondrial functionality, energy metabolism, and ultimately, color attributes. Postmortem yak longissimus thoracis et lumborum (LTL) muscles were incubated with saline, AMPK inhibitor (Compound C), Compound C plus HIF-1α activator (DMOG), and Compound C plus HIF-1α inhibitor (YC-1) for 0, 6, 12, 24, 72, and 120 h, respectively. Results indicate that Compound C hindered the nuclear translocation of HIF-1α (P < 0.001), in turn, DMOG upregulated AMPK protein levels (P < 0.05) by a yet unknown mechanism. Mass spectrometry analysis identified seven AMPK-induced phosphorylation sites (Ser58, Thr63, Ser65, Tyr66, Thr677, Ser14, and Ser15) mapped onto three phosphopeptides on HIF-1α. Moreover, Compound C induced a significant reduction in energy metabolism levels, evidenced by decreased glycogen degradation, lactate accumulation, and pH decline (P < 0.05). Besides, Compound C promoted a consistently decreased mitochondrial protein yield, reduced NADH content, and OCR (P < 0.05). However, DMOG attenuated the effects of Compound C on mitochondrial efficiency, and interconversion of oxy-to deoxymyoglobin. Collectively, these findings establish the collaborative influence of AMPK and HIF-1α on postmortem energy metabolism, concurrently emphasizing their antagonistic effects on mitochondrial function.