RRC ID 62311
Author Wilden AR, Molina JA, Feuerborn M, Boyle D, Lee SY.
Title Glutamine-dependent lysosome homeostatic changes induced by starvation and lysosome inhibition.
Journal Biochim Biophys Acta Mol Cell Res
Abstract Lysosomes are a major organelle for degrading macromolecules. When deprived of nutrients, cells activate the autophagy and lysosome biogenesis pathways to recycle cytoplasmic materials and to increase lysosomal degradation capacity for survival, respectively. We have identified a condition in which cells accumulated enlarged lysosomes upon starvation and lysosome inhibition. Selective autophagy and inhibition of the mechanistic target of rapamycin (mTOR) in combination with lysosome inhibition were not able to induce this phenomenon. Conversely, knocking out autophagy genes, ATG5 or ATG7, had no effects on the enlarged lysosome formation. This suggests that the enlarged lysosome formation is an autophagy independent process. Remarkably, adding glutamine to the treatment can prevent formation of the enlarged lysosomes and dissipate the pre-existing ones. Furthermore, the nucleus/cytoplasm translocation of the transcription factor EB (TFEB), but not mTOR activity, correlates with the formation/dissipation of enlarged lysosomes. Knockdown of TFEB, however, suggests that TFEB-mediated lysosome biogenesis is not directly involved in the process. These results indicate that there is a novel mechanism by which lysosome homeostasis can be regulated under certain stress conditions.
Volume 1865(9)
Pages 1356-1367
Published 2018-9-1
DOI 10.1016/j.bbamcr.2018.06.014
PII S0167-4889(18)30144-7
PMID 29966622
PMC PMC6392085
MeSH Animals Autophagy Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism* Cell Line Glutamine / drug effects* HeLa Cells Homeostasis Humans Lysosomes / physiology* Mice TOR Serine-Threonine Kinases / antagonists & inhibitors TOR Serine-Threonine Kinases / metabolism*
IF 4.105
Human and Animal Cells Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711) Atg7 +/+ MEFs(RCB3706) Atg7 -/- MEFs(RCB3707)