The formation of autophagosomes during lysosomal defect: A new source of cytotoxicity

Macroautophagy/autophagy comprises autophagosome synthesis and lysosomal degradation. It is well known that lysosomal defects cause toxicity to cells. However, it has not been investigated previously if cytotoxicity is conferred by autophagosome formation during lysosomal defect. Recently, we found...

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Bibliographic Details
Published in:Autophagy 2017-10, Vol.13 (10), p.1797-1798
Main Authors: Button, Robert W., Luo, Shouqing
Format: Article
Language:English
Subjects:
Animals
Autophagic Punctum
autophagosome
Autophagosomes - physiology
autophagy
Autophagy - genetics
Autophagy - physiology
Cell Death - genetics
Cell Survival - genetics
cytotoxicity
Gene Knockdown Techniques
Humans
Lysosomes - genetics
Lysosomes - metabolism
Lysosomes - pathology
MTOR
Organelle Biogenesis
Qa-SNARE Proteins - genetics
STX17
TOR Serine-Threonine Kinases - genetics
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Summary:Macroautophagy/autophagy comprises autophagosome synthesis and lysosomal degradation. It is well known that lysosomal defects cause toxicity to cells. However, it has not been investigated previously if cytotoxicity is conferred by autophagosome formation during lysosomal defect. Recently, we found that the formation of autophagosomes in such conditions also causes cytotoxicity, in addition to lysosomal defect insults. We revealed that a partial reduction in autophagosome synthesis was beneficial for cell survival in cells bearing the autophagosome formation-based toxicity. Our study suggests that production/accumulation of autophagosomes during lysosomal defect directly induces cellular toxicity, and this process may be implicated in the pathological conditions where lysosomes are defective.
ISSN:1554-8627
1554-8635
DOI:10.1080/15548627.2017.1358850