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Updated: Oct 23, 2025
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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
Published on: April 1, 2011
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Frame-shifted APOBEC3A encodes two alternative proapoptotic proteins that target the mitochondrial network
Vincent Caval1, Rodolphe Suspène1, Pierre Khalfi2
1Molecular Retrovirology Unit, Institut Pasteur, Paris, France.
The Journal of Biological Chemistry
|August 17, 2021
Summary
The APOBEC3A gene encodes two distinct proteins: A3A, a DNA mutator, and novel A3Alt proteins that induce apoptosis by targeting mitochondria. This dual function highlights a new mechanism for programmed cell death.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- The human APOBEC3A (A3A) enzyme is a significant source of somatic mutations in tumor DNA.
- A discrepancy exists between APOBEC3A mRNA and protein levels in stimulated myeloid cells.
Purpose of the Study:
- Investigate the expression of novel alternative APOBEC3A proteins.
- Clarify the discrepancy in APOBEC3A expression levels.
Main Methods:
- Analysis of alternative reading frames within the APOBEC3A gene.
- Characterization of novel protein isoforms and their cellular localization.
- Assessment of mitochondrial targeting and apoptotic effects.
Main Results:
- Identified two novel alternative proteins, A3Alt-L and A3Alt-S, from the APOBEC3A gene.
- A3Alt proteins are transmembrane and localize to mitochondria.
- A3Alt proteins induce mitochondrial membrane depolarization and apoptosis.
Conclusions:
- The APOBEC3A gene encodes both DNA-targeting cytidine deaminase (A3A) and mitochondria-targeting proapoptotic proteins (A3Alt).
- This discovery reveals a single gene's capacity to produce proteins with distinct cellular functions and roles in apoptosis.
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