Autophagy is a catabolic pathway in which the cell sequesters cytoplasmic material, including long-lived proteins, lipids and organelles, in specialized double-membrane vesicles, called autophagosomes. Subsequently, autophagosomes communicate with the lysosomal compartment and acquire acidic hydrolases for final cargo degradation. This process of partial self-eating secures the survival of eukaryotic cells during starvation periods and is critically regulated by mTORC1 (mammalian target of rapamycin complex 1). Under nutrient-poor conditions, inhibited mTORC1 permits localized PtdIns(3)P production at particular membranes that contribute to autophagosome formation. Members of the human WIPI (WD-repeat protein interacting with phosphoinositides) family fulfil an essential role as PtdIns(3)P effectors at the initiation step of autophagosome formation. In the present article, we discuss the role of human WIPIs in autophagy, and the identification of evolutionarily conserved amino acids of WIPI-1 that confer PtdIns(3)P binding downstream of mTORC1 inhibition. We also discuss the PtdIns(3)P effector function of WIPIs in the context of longevity and autophagy-related human diseases, such as cancer and neurodegeneration.
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August 2013
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Conference Article|
July 18 2013
WIPI β-propellers in autophagy-related diseases and longevity
Daniela Bakula;
Daniela Bakula
1Autophagy Laboratory, Interfaculty Institute of Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany
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Zsuzsanna Takacs;
Zsuzsanna Takacs
1Autophagy Laboratory, Interfaculty Institute of Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany
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Tassula Proikas-Cezanne
Tassula Proikas-Cezanne
1
1Autophagy Laboratory, Interfaculty Institute of Cell Biology, Eberhard Karls University Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany
1To whom correspondence should be addressed (emailtassula.proikas-cezanne@uni-tuebingen.de).
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Publisher: Portland Press Ltd
Received:
April 02 2013
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (4): 962–967.
Article history
Received:
April 02 2013
Citation
Daniela Bakula, Zsuzsanna Takacs, Tassula Proikas-Cezanne; WIPI β-propellers in autophagy-related diseases and longevity. Biochem Soc Trans 1 August 2013; 41 (4): 962–967. doi: https://doi.org/10.1042/BST20130039
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