mTOR-Controlled Autophagy Requires Intracellular Ca2+ Signaling

Autophagy is a lysosomal degradation pathway important for cellular homeostasis and survival. Inhibition of the mammalian target of rapamycin (mTOR) is the best known trigger for autophagy stimulation. In addition, intracellular Ca2+ regulates autophagy, but its exact role remains ambiguous. Here, w...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e61020
Main Authors: Decuypere, Jean-Paul, Kindt, Dimphny, Luyten, Tomas, Welkenhuyzen, Kirsten, Missiaen, Ludwig, De Smedt, Humbert, Bultynck, Geert, Parys, Jan B.
Format: Article
Language:English
Subjects:
Autophagy
Biology
Calcium (intracellular)
Calcium buffering
Calcium channels
Calcium release channels
Calcium signalling
Cell death
Cell survival
Homeostasis
Inositol 1,4,5-trisphosphate receptors
Intracellular
Intracellular signalling
Kinases
Laboratories
Leak channels
Lysosomes
Machinery and equipment
Medical research
Medicine
Phagocytosis
Proteins
Rapamycin
Receptors
Signal transduction
TOR protein
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Summary:Autophagy is a lysosomal degradation pathway important for cellular homeostasis and survival. Inhibition of the mammalian target of rapamycin (mTOR) is the best known trigger for autophagy stimulation. In addition, intracellular Ca2+ regulates autophagy, but its exact role remains ambiguous. Here, we report that the mTOR inhibitor rapamycin, while enhancing autophagy, also remodeled the intracellular Ca2+-signaling machinery. These alterations include a) an increase in the endoplasmic-reticulum (ER) Ca2+-store content, b) a decrease in the ER Ca2+-leak rate, and c) an increased Ca2+ release through the inositol 1,4,5-trisphosphate receptors (IP3Rs), the main ER-resident Ca2+-release channels. Importantly, buffering cytosolic Ca2+ with BAPTA impeded rapamycin-induced autophagy. These results reveal intracellular Ca2+ signaling as a crucial component in the canonical mTOR-dependent autophagy pathway.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0061020