A comprehensive systems biological study of autophagy-apoptosis crosstalk during endoplasmic reticulum stress

Marianna Holczer, Margita Márton, Anita Kurucz, G. Bánhegyi, O. Kapuy

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Article number319589
JournalBioMed Research International
Volume2015
DOIs
Publication statusPublished - 2015

Fingerprint

Endoplasmic Reticulum Stress
Autophagy
Biological systems
Crosstalk
Endoplasmic Reticulum
Apoptosis
Chemical activation
Cell death
Metabolism
Switches
Feedback
Homeostasis
Cell Death
Population

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

A comprehensive systems biological study of autophagy-apoptosis crosstalk during endoplasmic reticulum stress. / Holczer, Marianna; Márton, Margita; Kurucz, Anita; Bánhegyi, G.; Kapuy, O.

In: BioMed Research International, Vol. 2015, 319589, 2015.

Research output: Contribution to journalArticle

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