A new role for ATM: regulating mitochondrial function and mitophagy.
The various pathologies in ataxia telangiectasia (A-T) patients including T-cell lymphomagenesis have been attributed to defects in the DNA damage response pathway because ATM, the gene mutated in this disease, is a key mediator of this process. Analysis of Atm-deficient thymocytes in mice reveals that the absence of this gene results in altered mitochondrial homeostasis, a phenomenon that appears to result from abnormal mitophagy engagement. Interestingly, allelic loss of the autophagic gene Becn1 delays tumorigenesis in Atm-null mice presumably by reversing the mitochondrial abnormalities and not by improving the DNA damage response (DDR) pathway. Thus, ATM plays a critical role in modulating mitochondrial homeostasis perhaps by regulating mitophagy.
Duke Scholars
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Related Subject Headings
- Ubiquitin-Protein Ligases
- Tumor Suppressor Proteins
- Protein Serine-Threonine Kinases
- Oxidative Stress
- Mitochondria
- Mice
- Membrane Potential, Mitochondrial
- Humans
- Fibroblasts
- DNA-Binding Proteins
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Ubiquitin-Protein Ligases
- Tumor Suppressor Proteins
- Protein Serine-Threonine Kinases
- Oxidative Stress
- Mitochondria
- Mice
- Membrane Potential, Mitochondrial
- Humans
- Fibroblasts
- DNA-Binding Proteins