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Updated: Apr 23, 2026

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Mitochondrial AK3 inhibits nuclear β-catenin localization and its activation through enhancing mitochondrial activity

Muhah Jeong1, Shin-Hyeon Ryu1, Young-Sin Cho1

  • 1School of Biological Sciences, Seoul National University, Seoul, South Korea.

Cell Death & Disease
|April 21, 2026
PubMed

Insights

Mitochondrial adenylate kinase 3 (AK3) regulates Wnt/β-catenin signaling by controlling nuclear β-catenin accumulation. AK3 activity inhibits cancer cell proliferation by modulating interactions between β-catenin and mitofusins.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Cancer Biology

Background:

  • Aberrant Wnt/β-catenin signaling is linked to developmental disorders and cancer.
  • The precise spatial regulation of cytoplasmic β-catenin's nuclear entry and signaling activation is not fully understood.

Purpose of the Study:

  • To investigate the role of mitochondrial adenylate kinase 3 (AK3) in regulating Wnt/β-catenin signaling.
  • To elucidate the mechanism by which AK3 influences nuclear β-catenin localization and activation.

Main Methods:

  • Transcriptome profiling of cancer patient datasets.
  • Analysis of cancer cell lines.
  • Identification of protein interactors using co-immunoprecipitation and other assays.

Main Results:

  • Mitochondrial AK3, involved in the TCA cycle, regulates nuclear β-catenin localization and activation.
  • AK3 enzymatic activity inhibits Wnt/β-catenin signaling and cell proliferation by reducing nuclear β-catenin.
  • Mitofusins (MFN1 & 2) were identified as key interactors mediating AK3's regulation of β-catenin signaling.
  • AK3 enhances β-catenin-mitofusins interactions, which are disrupted by CCCP treatment.

Conclusions:

  • Metabolically active mitochondria, induced by AK3, restrain Wnt/β-catenin signaling.
  • AK3 modulates β-catenin signaling through its interactions with mitofusins, impacting cancer cell proliferation.

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