Axin Is Localized within Mitochondria and Regulates Energy Metabolism through Alterations of Oxidative Phosphorylation and Glycolysis

Axin is a scaffolding protein that antagonizes Wnt signaling and controls various cellular events, involving cell proliferation and death. Tankyrase inhibitors, such as XAV939 stabilizes the axin protein, provide a therapeutic strategy for cancers. To study effects of axin expression on mitochondria, we established two axin‐expressing HeLa cells models: doxycycline‐inducible axin expression and enhanced axin expression by treatment with XAV939. Axin‐expressing cells showed localization of axin in mitochondria, especially the oxidative phosphorylation (OXPHOS) complex IV. Axin reduced complex IV subunits expression and altered supercomplexes formation. Moreover, axin led to functional alteration containing the reduction of cell proliferation, ATP level, complex IV activity, and basal respiration. Despite the respiratory effects, the glycolysis was increased and mitochondrial membrane potential was maintained, which even preserved in the presence of mitochondria‐affecting stimuli in axin‐expressing cells. In conclusion, our results suggest that axin was expressed in complex IV of mitochondria, which modulated mitochondrial function and glycolysis.