Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria
Ellen Wirawan,L Vande Walle,Kristof Kersse,Sigrid Cornelis,Sigrid Cornelis,Sofie Claerhout,Isabel Vanoverberghe,Ria Roelandt,R. De Rycke,Jelle Verspurten,Wim Declercq,Patrizia Agostinis,T Vanden Berghe,Saskia Lippens,Peter Vandenabeele +14 more
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TLDR
Findings point to a mechanism by which casp-dependent generation of Beclin-1-C creates an amplifying loop enhancing apoptosis upon growth factor withdrawal.Abstract:
Autophagy and apoptosis are two important and interconnected stress-response mechanisms. However, the molecular interplay between these two pathways is not fully understood. To study the fate and function of autophagic proteins at the onset of apoptosis, we used a cellular model system in which autophagy precedes apoptosis. IL-3 depletion of Ba/F3 cells caused caspase (casp)-mediated cleavage of Beclin-1 and PI3KC3, two crucial components of the autophagy-inducing complex. We identified two casp cleavage sites in Beclin-1, TDVD133 and DQLD149, cleavage at which yields fragments lacking the autophagy-inducing capacity. Noteworthy, the C-terminal fragment, Beclin-1-C, localized predominantly at the mitochondria and sensitized the cells to apoptosis. Moreover, on isolated mitochondria, recombinant Beclin-1-C was able to induce the release of proapoptotic factors. These findings point to a mechanism by which casp-dependent generation of Beclin-1-C creates an amplifying loop enhancing apoptosis upon growth factor withdrawal.read more
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Autophagy and the Integrated Stress Response
TL;DR: Autophagy is a cell biological process that is a central component of the integrated stress response and can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli.
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Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
Lorenzo Galluzzi,Ilio Vitale,Ilio Vitale,Ilio Vitale,John M. Abrams,Emad S. Alnemri,Eric H. Baehrecke,Mikhail V. Blagosklonny,Ted M. Dawson,Valina L. Dawson,Wafik S. El-Deiry,Simone Fulda,Eyal Gottlieb,Douglas R. Green,Michael O. Hengartner,Oliver Kepp,Oliver Kepp,Oliver Kepp,Richard A. Knight,Sharad Kumar,Sharad Kumar,Stuart A. Lipton,Xin Lu,Frank Madeo,Walter Malorni,Patrick Mehlen,Gabriel Núñez,Marcus E. Peter,Mauro Piacentini,David C. Rubinsztein,Yufang Shi,Hans-Uwe Simon,Peter Vandenabeele,Eileen White,Junying Yuan,Boris Zhivotovsky,Gerry Melino,Gerry Melino,Guido Kroemer +38 more
TL;DR: A functional classification of cell death subroutines is proposed that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic programmed cell death, regulated necrosis, autophagic cell death and mitotic catastrophe.
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TL;DR: The recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy is reviewed, focusing on the relevance and impact of this crosstalk in normal development and in pathology.
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References
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Journal ArticleDOI
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Sophie Pattingre,Sophie Pattingre,Amina T. Tassa,Xueping Qu,Xueping Qu,Rita Garuti,Xiao Huan Liang,Noboru Mizushima,Milton Packer,Michael D. Schneider,Beth Levine,Beth Levine +11 more
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Journal ArticleDOI
Regulation Mechanisms and Signaling Pathways of Autophagy
Congcong He,Daniel J. Klionsky +1 more
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