The DOI matches its Crossref record; 49 of the 51 references it cites were found in a registry or an index.
Mitochondrial dysfunction in ataxia-telangiectasia
Open accessAbstract
Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies. Here, we show that ATM loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including elevated reactive oxygen species, increased aberrant mitochondria, high cellular respiratory capacity, and decreased mitophagy. A fraction of ATM protein is localized in mitochondria, and it is rapidly activated by mitochondrial dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1 significantly delayed tumor development in ATM-null mice. This effect was not associated with rescue of DNA damage signaling but rather with a significant reversal of the mitochondrial abnormalities. These data support a model in which ATM plays direct roles in modulating mitochondrial homeostasis and suggest that mitochondrial dysfunction and associated increases in mitochondrial reactive oxygen species contribute to the cancer-prone phenotype observed in organisms lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part, as a mitochondrial disease.
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“Analysis of an ATM mouse model showed dysfunctional mitochondria with increased ROS levels and the accumulation of damaged mitochondria87.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [87]
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Methods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497
Youle, R. J., & Narendra, D. P. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3028 · Cited by 3,273
Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene
Qu, X., Yu, J., Bhagat, G., Furuya, N., Hibshoosh, H., Troxel, A., Rosen, J., Eskelinen, E.-L., Mizushima, N., Ohsumi, Y., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci20039 · Cited by 2,311
Yue, Z., Jin, S., Yang, C., Levine, A. J., & Heintz, N. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2436255100 · Cited by 2,116
Rabinowitz, J. D., & White, E. (2010) · Science · doi:10.1126/science.1193497 · Cited by 1,982
Mathew, R., Karantza-Wadsworth, V., & White, E. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2254 · Cited by 1,798
The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice
Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., Palmiter, R. D., & Brinster, R. L. (1985) · Nature · doi:10.1038/318533a0 · Cited by 1,779
Atm-Deficient Mice: A Paradigm of Ataxia Telangiectasia
Barlow, C., Hirotsune, S., Paylor, R. E., Liyanage, M., Eckhaus, M., Collins, F. S., Shiloh, Y., Crawley, J. N., Ried, T., Tagle, D. A., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)80086-0 · Cited by 1,465
Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells
Ito, K., Hirao, A., Arai, F., Takubo, K., Matsuoka, S., Miyamoto, K., Ohmura, M., Naka, K., Hosokawa, K., Ikeda, Y., et al. (2006) · Nature Medicine · doi:10.1038/nm1388 · Cited by 1,362
Regulation of pgc-1α, a nodal regulator of mitochondrial biogenesis
Fernandez-Marcos, P. J., & Auwerx, J. (2011) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.001917 · Cited by 1,237
Cited by
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Ageing as a risk factor for neurodegenerative disease
Hou, Y., Dan, X., Babbar, M., Wei, Y., Hasselbalch, S. G., Croteau, D. L., & Bohr, V. A. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0244-7 · Cited by 3,310
ROS and the DNA damage response in cancer
Srinivas, U. S., Tan, B. W. Q., Vellayappan, B. A., & Jeyasekharan, A. D. (2019) · Redox Biology · doi:10.1016/j.redox.2018.101084 · Cited by 2,144
“ATM loss modulates mitochondrial turnover, with an increase in aberrant mitochondria and therefore ROS [40,41].”
BackgroundDeconvoluting the context-dependent role for autophagy in cancer
White, E. (2012) · Nature reviews. Cancer · doi:10.1038/nrc3262 · Cited by 1,758
The ATM protein kinase: regulating the cellular response to genotoxic stress, and more
Shiloh, Y., & Ziv, Y. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3546 · Cited by 1,649
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Rubinsztein, D. C., Codogno, P., & Levine, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3802 · Cited by 1,464
Metadata
- Authors
- Valentin-Vega, Y. A., MacLean, K. H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F. C., Cleveland, J. L., Green, D. R., & Kastan, M. B.
- Affiliations
- Departments of Oncology and
- St. Jude Children's Research Hospital (US)
- Scripps Research Institute (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2012-02-09
- Volume
- 119
- Issue
- 6
- Pages
- 1490-1500
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC3286212
- OpenAlex
- W2120886826
- Cited by
- 365
- References
- 51
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 20 · 2023: 17 · 2022: 22 · 2021: 46 · 2020: 30 · 2019: 26 · 2018: 15 · 2017: 29 · 2016: 38 · 2015: 25 · 2014: 27 · 2013: 29 · 2012: 17
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA076379, R01CA157216, CA71387, CA157216, R01CA076379, P 30CA 21765, R01CA071387, P30CA021765)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ataxia telangiectasia, ATM, mitochondrial dysfunction, thymocytes, reactive oxygen species, mitophagy, cellular respiration, Beclin-1, autophagy, DNA damage response, T-cell malignancies, mitochondrial homeostasis, cancer susceptibility
- MeSH terms
- Beclin-1, Adenosine Triphosphate, Animals, Ataxia Telangiectasia, Autophagy, Cells, Cultured, DNA-Binding Proteins, Fibroblasts, Humans, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Oxygen Consumption, Immunoblotting, Gene Expression, Lymphoma, T-Cell, Protein Serine-Threonine Kinases, Reactive Oxygen Species, Mice, Knockout, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, RNA Interference, Microscopy, Electron, Transmission, Apoptosis Regulatory Proteins, Mice, Membrane Potential, Mitochondrial, Kaplan-Meier Estimate, Thymocytes, Ataxia Telangiectasia Mutated Proteins
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