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Intracellular calcium: a dual role in autophagy

Chehab, Tala; Rietdorf, Katja; Parys, Jan B. ; Bultynck, Geert and Bootman, Martin (2016). Intracellular calcium: a dual role in autophagy. In: Evolution brings Ca2+ and ATP together to control life and death, 16 - 17th March 2016, Chichley Hall, Newport Pagnell.

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Abstract

Autophagy leads to degradation of misfolded proteins and dysfunctional organelles and is enhanced by nutrient starvation, or rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR). Calcium has been proposed to act as both a positive and negative regulator of autophagy. We have investigated the sources and characteristics of calcium signals that affect autophagy induction.
Preventing calcium release from inositol 1,4,5-trisphosphate receptors (InsP3Rs), or inhibiting mitochondrial respiration with oligomycin and antimycin, enhanced autophagy in HEK and HeLa cells. These results suggest that calcium signals are necessary to prevent the induction of autophagy, and are consistent with the proposal that calcium flux from InsP3Rs to the mitochondrial matrix leads to ATP production that prevents the activation of autophagy.
In contrast, evoking long-lasting cytosolic calcium signals by either inhibiting SERCA pumps with cyclopiazonic acid, or application of ionomycin, in calcium-containing medium triggered autophagy. Moreover, buffering cytosolic calcium signals with BAPTA inhibited basal and rapamycin-evoked autophagy. These results suggest that calcium signals are necessary for the induction of autophagy, and that the ER is not a necessary calcium source.

Our study supports the dual nature of calcium as a regulator of autophagy. The identity of the processes affected by calcium are under investigation.

Item Type: Conference or Workshop Item
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Interdisciplinary Research Centre: Biomedical Research Network (BRN)
Health and Wellbeing PRA (Priority Research Area)
Item ID: 46040
Depositing User: Katja Rietdorf
Date Deposited: 14 Apr 2016 10:09
Last Modified: 11 Sep 2017 15:32
URI: http://oro.open.ac.uk/id/eprint/46040
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