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Related Experiment Video

Updated: May 17, 2026

Examining BCL-2 Family Function with Large Unilamellar Vesicles

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Published on: October 5, 2012

Sirtuin-3 modulates Bak- and Bax-dependent apoptosis.

Manish Verma¹, Nataly Shulga, John G Pastorino

¹Department of Molecular Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, NJ 08084, USA.

Journal of Cell Science

|October 31, 2012

Summary

Sirtuin-3 depletion promotes cancer cell survival by preventing mitochondrial damage through increased cyclophilin-D activity. Conversely, higher sirtuin-3 levels enhance cell death by reducing this activity.

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Published on: January 12, 2016

Area of Science:

Mitochondrial Metabolism
Cancer Biology
Cell Death Pathways

Background:

Sirtuin-3 (SIRT3) acts as a tumor suppressor by regulating mitochondrial metabolism.
SIRT3 depletion is linked to increased tumor cell survival.
The precise mechanisms by which SIRT3 influences cell death remain under investigation.

Purpose of the Study:

To elucidate the role of Sirtuin-3 in regulating apoptosis and mitochondrial integrity.
To investigate the involvement of cyclophilin-D, hexokinase II, and Bak/Bax in SIRT3-mediated cell death.

Main Methods:

Cellular assays to assess apoptosis and mitochondrial injury.
Analysis of cyclophilin-D activity.
Investigation of hexokinase II binding to mitochondria.
Evaluation of Bak/Bax protein activity.

Main Results:

Sirtuin-3 depletion stimulates cyclophilin-D activity, promoting hexokinase II binding to mitochondria.
This binding prevents Bak/Bax-dependent mitochondrial injury and cell death, conferring an anti-apoptotic phenotype.
Increased Sirtuin-3 expression reduces cyclophilin-D activity, detaching hexokinase II and sensitizing cells to apoptosis.

Conclusions:

Sirtuin-3 critically regulates cell viability by modulating mitochondrial pathways.
The SIRT3-cyclophilin-D-hexokinase II axis is a key determinant of mitochondrial injury and apoptosis.
Targeting this pathway may offer therapeutic strategies for cancer treatment.