Axin is expressed in mitochondria and suppresses mitochondrial ATP synthesis in HeLa cells

Jee-Hye Shin1, Hyun-Wook Kim2, Im Joo Rhyu2

  • 1Department of Microbiology, College of Medicine, Korea University, Seoul 136-705, Korea.

Experimental Cell Research
|December 26, 2015
PubMed

Insights

Axin protein suppresses cellular ATP production by disrupting mitochondrial oxidative phosphorylation complex IV. This finding reveals a novel role for axin in regulating mitochondrial function and cellular energy.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Axin is known for its role in Wnt signaling.
  • Previous observations suggested a link between axin and mitochondria.
  • The precise function of axin in mitochondria remains largely unexplored.

Purpose of the Study:

  • To investigate the relationship between axin and mitochondrial function.
  • To determine the impact of axin expression on cellular energy production.
  • To elucidate the molecular mechanisms underlying axin's mitochondrial effects.

Main Methods:

  • Utilized doxycycline-inducible HeLa cell models (HeLa-axin) and XAV939-treated HeLa cells (HeLa-XAV) to study axin expression.
  • Performed biochemical analyses to assess axin's association with oxidative phosphorylation (OXPHOS) complex IV.
  • Measured cellular ATP production, OXPHOS complex IV activity, and oxygen consumption rate (OCR).

Main Results:

  • Increased axin expression suppressed cellular ATP production in a dose-dependent manner.
  • Axin was found to associate with OXPHOS complex IV, leading to assembly defects.
  • Axin expression reduced OXPHOS complex IV activity and OCR, indicating mitochondrial dysfunction.
  • XAV939 treatment impacted ATP synthesis beyond Wnt signaling inhibition.

Conclusions:

  • Axin expression leads to mitochondrial dysfunction by impairing OXPHOS complex IV.
  • Axin's regulation of mitochondrial function represents a novel mechanism potentially influencing cell growth.
  • These findings expand the known cellular roles of axin beyond Wnt signaling.

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