MTOR-Controlled Autophagy Requires Intracellular Ca(2+) Signaling

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Apr 9

PMID 23565295

Citations 53

Authors

Jean-Paul Decuypere

Dimphny Kindt

Tomas Luyten

Kirsten Welkenhuyzen

Ludwig Missiaen

Humbert De Smedt

Geert Bultynck

Jan B Parys

Affiliations

Soon will be listed here.

Abstract

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 Ca(2+) regulates autophagy, but its exact role remains ambiguous. Here, we report that the mTOR inhibitor rapamycin, while enhancing autophagy, also remodeled the intracellular Ca(2+)-signaling machinery. These alterations include a) an increase in the endoplasmic-reticulum (ER) Ca(2+)-store content, b) a decrease in the ER Ca(2+)-leak rate, and c) an increased Ca(2+) release through the inositol 1,4,5-trisphosphate receptors (IP3Rs), the main ER-resident Ca(2+)-release channels. Importantly, buffering cytosolic Ca(2+) with BAPTA impeded rapamycin-induced autophagy. These results reveal intracellular Ca(2+) signaling as a crucial component in the canonical mTOR-dependent autophagy pathway.

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