AUTOPHAGY: Autophagy enhancement causes complaccision.

Co-dysfunction is an autosomal recessive disease characterized by a cosmologic disorder, accompanied by cer cerebral psychic cell degeneration, immunodeficiency, vulnerability to X-rays, susceptible to cancer, infertility and other symptoms.
it is caused by a single gene, ATM (a mutation in the free-range endoenzythrosis), which encodes proteins that are members of a 370kDa family of phosphatidyl inositol3 kinase-related kinases (PIKK).
ATM and its PIKK sister kinase ATR (associated with co-dysfunctional telomere disease and Rad3) play a role in DNA damage responses.
ATR is mainly involved in the repair of single-stranded DNA fractures, while ATMs are more involved in the repair of double-stranded fractures.
A-T esopaedics appear to be associated with DNA damage repair (radiation sensitivity and cancer proneness).
, however, we don't know much about neurological defects, including how DNA repair damage can lead to clinical symptoms of A-T.
in addition to playing a role in dna damage repair in the nuclei of cells, ATMs and ATRs are also present in the cytoste.
peroxidases, synthosomes, and lysosomes are all associated with ATM proteins.
addition, glucose transporter is also the target of ATM kinase, suggesting that ATM may have an extra-nuclear effect in regulating glucose metabolism.
recently, researchers published a paper in the journal Autophagy, reporting that part of the reason for the complex ideotypes of A-T caused by ATM mutations may be autophagy and lysosome abnormalities.
researchers found that ATMs degrade through autophagy, while ATR degrades by protease processing.
autophagy and lysosome transport are abnormal in atm-/- neurons, and the defect affects cellular functions such as synth maintenance, neuron survival, and glucose intake.
in atm-/- lysosomes, the researchers observed an increase in autophagy, which is associated with a more acidic pH.
important, the researchers found that the ATP6V1A (ATP enzyme, H-transport, lysosome V1 sub-base A) proton pump is the target of ATM kinase.
in atm-/- neurons, lysosomes exhibit enhanced retrograde transport and are concentrated in the nuclear pervezion region.
researchers attribute this change to an unexpected physical interaction between ATM and retrograde transport motor protein dynein.
Therefore, this effect inhibits the transport of SLC2A4 / GLUT4 (solute vector family 4 (promoted glucose transport protein, member 4) to the mass membrane, and increases its transport to the lysosome, resulting in impaired glucose intake capacity.
, the data highlight attned to ATM's involvement in the transport of various neuron bubbles, providing new insights into the pathogenesis of A-T and possibly helping to develop new treatments.
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