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The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

AMPK-independent induction of autophagy by cytosolic Ca2+ increase

Grotemeier, Antje, Alers, Sebastian, Pfisterer, Simon G., Paasch, Florian, Daubrawa, Merle, Dieterle, Alexandra, Viollet, Benoit, Wesselborg, Sebastian, Proikas-Cezanne, Tassula, Stork, Björn·2010·Cellular Signalling
DOI 10.1016/j.cellsig.2010.01.015
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Abstract

Autophagy is a eukaryotic lysosomal bulk degradation system initiated by cytosolic cargo sequestration in autophagosomes. The Ser/Thr kinase mTOR has been shown to constitute a central role in controlling the initiation of autophagy by integrating multiple nutrient-dependent signaling pathways that crucially involves the activity of PI3K class III to generate the phosphoinositide PI(3)P. Recent reports demonstrate that the increase in cytosolic Ca(2+) can induce autophagy by inhibition of mTOR via the CaMKK-alpha/beta-mediated activation of AMPK. Here we demonstrate that Ca(2+) signaling can additionally induce autophagy independently of the Ca(2+)-mediated activation of AMPK. First, by LC3-II protein monitoring in the absence or presence of lysosomal inhibitors we confirm that the elevation of cytosolic Ca(2+) induces autophagosome generation and does not merely block autophagosome degradation. Further, we demonstrate that Ca(2+)-chelation strongly inhibits autophagy in human, mouse and chicken cells. Strikingly, we found that the PI(3)P-binding protein WIPI-1 (Atg18) responds to the increase of cytosolic Ca(2+) by localizing to autophagosomal membranes (WIPI-1 puncta) and that Ca(2+)-chelation inhibits WIPI-1 puncta formation, although PI(3)P-generation is not generally affected by these Ca(2+) flux modifications. Importantly, using AMPK-alpha1(-/-)alpha2(-/-) MEFs we show that thapsigargin application triggers autophagy in the absence of AMPK and does not involve complete…

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Research works printed but not linked: 24

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Metadata

Authors
Grotemeier, A., Alers, S., Pfisterer, S. G., Paasch, F., Daubrawa, M., Dieterle, A., Viollet, B., Wesselborg, S., Proikas-Cezanne, T., & Stork, B.
Venue
Cellular Signalling
Publisher
Elsevier BV
Published
2010-06
Volume
22
Issue
6
Pages
914-925
ISSN
0898-6568
DOI
10.1016/j.cellsig.2010.01.015
Cited by
143
References
8
Language
en
Licence

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