Abstract:
:One of the most important tasks of a living organism is to maintain its genetic integrity with respect to stress. Endoplasmic reticulum (ER) has a crucial role in sensing cellular homeostasis by controlling metabolism, proteostasis, and several signaling processes. ER stressors can induce autophagy-dependent survival; however excessive level of stress results in apoptotic cell death. Although many molecular components of these networks have already been discovered, the analysis of the dynamical features of the regulatory network of life-or-death decision is still lacking. Our goal was to incorporate both theoretical and molecular biological techniques to explore the autophagy-apoptosis crosstalk under ER stress. Using various levels of different ER stressors we confirmed that the control network always generated an evidently detectable autophagy-dependent threshold for apoptosis activation. We explored the features of this threshold by introducing both autophagy activators and inhibitors, and transient treatment with excessive level of ER stressor was also performed. Our experimental data were also supported by a stochastic approach. Our analysis suggests that even if the switch-like characteristic of apoptosis activation is hardly seen on population level the double negative feedback loop between autophagy and apoptosis inducers introduces bistability in the control network.
journal_name
Biomed Res Intjournal_title
BioMed research internationalauthors
Holczer M,Márton M,Kurucz A,Bánhegyi G,Kapuy Odoi
10.1155/2015/319589subject
Has Abstractpub_date
2015-01-01 00:00:00pages
319589eissn
2314-6133issn
2314-6141journal_volume
2015pub_type
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2015/457473
更新日期:2015-01-01 00:00:00
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pub_type: 杂志文章,多中心研究
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pub_type: 杂志文章,评审
doi:10.1155/2014/780752
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pub_type: 杂志文章,评审
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更新日期:2015-01-01 00:00:00
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doi:10.1155/2017/9491045
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更新日期:2020-03-30 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
doi:10.1155/2014/540238
更新日期:2014-01-01 00:00:00
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doi:10.1155/2014/429198
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pub_type: 杂志文章
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