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  4. CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore

CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore

Advanced Science, 2024 · DOI: 10.1002/advs.202403093 · Published: June 19, 2024

OncologyAgingGenetics

Simple Explanation

Creatine kinases (CKs) are important for keeping a cell's energy in balance. They move a phosphoryl group from ATP to creatine. This study found that creatine kinases (CKMT1A, CKMT1B, and CKB) are highly expressed in cells that depend on mitochondrial ATP. The study found that silencing CKB leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in cells, indicating CKB's importance in mitochondrial function. CKB helps mitochondria produce ATP by lowering mitochondrial calcium levels, which prevents the mitochondrial permeability transition pore (mPTP) from activating. This ensures mitochondria can efficiently generate ATP.

Study Duration
Not specified
Participants
23 healthy individuals aged 20–29 (Young group) and thirty sex-matched healthy individuals aged 50–59 (Aged group)
Evidence Level
Not specified

Key Findings

  • 1
    CKB is essential for maintaining cellular sensitivity to F1F0 ATP synthase inhibition, a key enzyme in mitochondrial ATP production.
  • 2
    CKB deficiency impairs mitochondrial ATP production, leading to increased reliance on glycolysis for energy production.
  • 3
    CKB suppresses mitochondrial calcium levels and mPTP activity, promoting efficient mitochondrial ATP production.

Research Summary

This study reveals that CKB promotes mitochondrial ATP production by inhibiting AKT activation, which in turn reduces mitochondrial calcium levels and mPTP activity. The CKB-AKT signaling axis plays a crucial role in modulating mitochondrial ATP production in vivo, affecting tumor growth and potentially aging. The findings suggest that CKB's regulation of mitochondrial ATP generation is involved in cancer progression and aging, offering potential therapeutic targets.

Practical Implications

Cancer Therapy

CKB could be a biomarker for identifying cancer cells sensitive to mitochondrial ATP inhibitors.

Anti-aging Strategies

Maintaining CKB expression levels may help preserve mitochondrial function and reduce age-related decline.

Drug Development

Targeting the CKB-AKT signaling pathway could offer new therapeutic approaches for diseases related to mitochondrial dysfunction.

Study Limitations

  • 1
    The precise mechanism through which CKB suppresses AKT activation remains elusive.
  • 2
    Further research is needed to fully elucidate the role of phosphocreatine in CKB-mediated AKT signaling.
  • 3
    The study primarily focuses on cancer cell lines; further investigation is required to validate the findings in other cell types and tissues.

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