title: A new role for ATM: regulating mitochondrial function and mitophagy.
abstract: 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.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Yasmine A
authors.initials: YA
authors.lastname: Valentin-Vega
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kastan
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001343:Autophagy; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases