scholarly journals Sense and sensibility: ATM oxygen stress signaling manages brain cell energetics

2019 ◽  
Vol 218 (3) ◽  
pp. 732-734 ◽  
Author(s):  
Katharina Schlacher

The ataxia-telangiectasia mutated (ATM) gene regulates DNA damage repair, oxidative stress, and mitochondrial processes. In this issue, Chow et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201806197) connects ATM’s oxidative stress response functions to the sensing of metabolic ATP energetics distinctively important in high energy–demanding Purkinje brain cells, which could explain the most distinct A-T patient feature, cerebellar ataxia.

2014 ◽  
Vol 26 (6) ◽  
pp. 825-829 ◽  
Author(s):  
Xing-Yu Huang ◽  
Wichai Eungpinichpong ◽  
Atit Silsirivanit ◽  
Saowanee Nakmareong ◽  
Xiu-Hua Wu

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Marguerite Blignaut ◽  
Sarah Harries ◽  
Amanda Lochner ◽  
Barbara Huisamen

Ataxia Telangiectasia Mutated protein kinase (ATM) has recently come to the fore as a regulatory protein fulfilling many roles in the fine balancing act of metabolic homeostasis. Best known for its role as a transducer of DNA damage repair, the activity of ATM in the cytosol is enjoying increasing attention, where it plays a central role in general cellular recycling (macroautophagy) as well as the targeted clearance (selective autophagy) of damaged mitochondria and peroxisomes in response to oxidative stress, independently of the DNA damage response. The importance of ATM activation by oxidative stress has also recently been highlighted in the clearance of protein aggregates, where the expression of a functional ATM construct that cannot be activated by oxidative stress resulted in widespread accumulation of protein aggregates. This review will discuss the role of ATM in general autophagy, mitophagy, and pexophagy as well as aggrephagy and crosstalk between oxidative stress as an activator of ATM and its potential role as a master regulator of these processes.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1415
Author(s):  
Vittoria Cenni ◽  
Stefano Squarzoni ◽  
Manuela Loi ◽  
Elisabetta Mattioli ◽  
Giovanna Lattanzi ◽  
...  

Reactive Oxygen Species (ROS) are reactive molecules required for the maintenance of physiological functions. Oxidative stress arises when ROS production exceeds the cellular ability to eliminate such molecules. In this study, we showed that oxidative stress induces post-translational modification of the inner nuclear membrane protein emerin. In particular, emerin is phosphorylated at the early stages of the oxidative stress response, while protein phosphorylation is abolished upon recovery from stress. A finely tuned balance between emerin phosphorylation and O-GlcNAcylation seems to govern this dynamic and modulates emerin–BAF interaction and BAF nucleoplasmic localization during the oxidative stress response. Interestingly, emerin post-translational modifications, similar to those observed during the stress response, are detected in cells bearing LMNA gene mutations and are characterized by a free radical generating environment. On the other hand, under oxidative stress conditions, a delay in DNA damage repair and cell cycle progression is found in cells from Emery–Dreifuss Muscular Dystrophy type 1, which do not express emerin. These results suggest a role of the emerin–BAF protein platform in the DNA damage response aimed at counteracting the detrimental effects of elevated levels of ROS.


Blood ◽  
2013 ◽  
Vol 122 (19) ◽  
pp. 3322-3330 ◽  
Author(s):  
Paul S. Hole ◽  
Joanna Zabkiewicz ◽  
Chinmay Munje ◽  
Zarabeth Newton ◽  
Lorna Pearn ◽  
...  

Key Points More than 60% of primary AML blasts constitutively produce high levels of NOX-derived reactive oxygen species (ROS), which drives AML proliferation. High ROS AMLs show depleted antioxidant defenses but evade the oxidative stress response through suppression of p38MAPK signaling.


2013 ◽  
Vol 80 (1) ◽  
pp. 104-109 ◽  
Author(s):  
Ralf Moeller ◽  
Marina Raguse ◽  
Günther Reitz ◽  
Ryuichi Okayasu ◽  
Zuofeng Li ◽  
...  

ABSTRACTThe roles of various core components, including α/β/γ-type small acid-soluble spore proteins (SASP), dipicolinic acid (DPA), core water content, and DNA repair by apurinic/apyrimidinic (AP) endonucleases or nonhomologous end joining (NHEJ), inBacillus subtilisspore resistance to different types of ionizing radiation including X rays, protons, and high-energy charged iron ions have been studied. Spores deficient in DNA repair by NHEJ or AP endonucleases, the oxidative stress response, or protection by major α/β-type SASP, DPA, and decreased core water content were significantly more sensitive to ionizing radiation than wild-type spores, with highest sensitivity to high-energy-charged iron ions. DNA repair via NHEJ and AP endonucleases appears to be the most important mechanism for spore resistance to ionizing radiation, whereas oxygen radical detoxification via the MrgA-mediated oxidative stress response or KatX catalase activity plays only a very minor role. Synergistic radioprotective effects of α/β-type but not γ-type SASP were also identified, indicating that α/β-type SASP's binding to spore DNA is important in preventing DNA damage due to reactive oxygen species generated by ionizing radiation.


Reproduction ◽  
2000 ◽  
pp. 143-149 ◽  
Author(s):  
RM Sainz ◽  
RJ Reiter ◽  
JC Mayo ◽  
J Cabrera ◽  
DX Tan ◽  
...  

Pregnancy is a physiological state accompanied by a high energy demand of many bodily functions and an increased oxygen requirement. Because of the increased intake and utilization of oxygen, increased levels of oxidative stress would be expected. In the present study, the degree of lipid peroxidation was examined in different tissues from non-pregnant and pregnant rats after the delivery of their young. Melatonin and other indole metabolites are known to be direct free radical scavengers and indirect antioxidants. Thus the effect of pinealectomy at 1 month before pregnancy on the accumulation of lipid damage was investigated in non-pregnant and pregnant rats after the delivery of their young. Malonaldehyde and 4-hydroxyalkenal concentrations were measured in the lung, uterus, liver, brain, kidney, thymus and spleen from intact and pinealectomized pregnant rats soon after birth of their young and at 14 and 21 days after delivery. The same parameters were also evaluated in intact and pinealectomized non-pregnant rats. Shortly after delivery, lipid oxidative damage was increased in lung, uterus, brain, kidney and thymus of the mothers. No differences were detected in liver and spleen. Pinealectomy enhanced this effect in the uterus and lung. It is concluded that during pregnancy high levels of oxidative stress induce an increase in oxidative damage to lipids, which in some cases is inhibited by the antioxidative actions of pineal indoles.


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