Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Quantitative assessment of cell fate decision between autophagy and apoptosis

Bing Liu, Zoltán N. Oltvai, Hulya Bayir, Gary A. Silverman, Stephen C. Pak, David H. Perlmutter, Ivet Bahar
doi: https://doi.org/10.1101/129767
Bing Liu
1Departments of Computational Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zoltán N. Oltvai
1Departments of Computational Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
2Departments of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hulya Bayir
3Departments of Critical Care, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gary A. Silverman
4Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, MO 63110, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen C. Pak
5Departments of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David H. Perlmutter
4Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri, MO 63110, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivet Bahar
1Departments of Computational Systems Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: bahar@pitt.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Autophagy and apoptosis regulate cell survival and death, and are implicated in the pathogenesis of many diseases. The same type of stress signals can induce either process, but it is unclear how cells ‘assess’ cellular damage and make a ‘life’ or ‘death’ decision by activating autophagy or apoptosis. A computational model of coupled apoptosis and autophagy is built here to study the systems-level dynamics of the underlying signaling network. The model explains the differential dynamics of autophagy and apoptosis in response to various experimental stress signals. Autophagic response dominates at low-to-moderate stress; whereas the response shifts from autophagy (graded activation) to apoptosis (switch-like activation) with increasing intensity of stress. The model reveals that this dynamic cell fate decision is conferred by a core regulatory network involving cytoplasmic Ca2+ as a rheostat that fine-tunes autophagic and apoptotic responses. A G-protein signaling-mediated feedback loop maintains cytoplasmic Ca2+ level, which in turn governs autophagic response through an AMP-activated protein kinase (AMPK)-mediated feedforward loop. The model identified Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ) as a determinant of the opposite roles of cytoplasmic Ca2+ in autophagy regulation. The results also demonstrated that the model could contribute to the development of pharmacological strategies modulate cell fate decisions.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 23, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Quantitative assessment of cell fate decision between autophagy and apoptosis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Quantitative assessment of cell fate decision between autophagy and apoptosis
Bing Liu, Zoltán N. Oltvai, Hulya Bayir, Gary A. Silverman, Stephen C. Pak, David H. Perlmutter, Ivet Bahar
bioRxiv 129767; doi: https://doi.org/10.1101/129767
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Quantitative assessment of cell fate decision between autophagy and apoptosis
Bing Liu, Zoltán N. Oltvai, Hulya Bayir, Gary A. Silverman, Stephen C. Pak, David H. Perlmutter, Ivet Bahar
bioRxiv 129767; doi: https://doi.org/10.1101/129767

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4377)
  • Biochemistry (9568)
  • Bioengineering (7080)
  • Bioinformatics (24814)
  • Biophysics (12594)
  • Cancer Biology (9940)
  • Cell Biology (14328)
  • Clinical Trials (138)
  • Developmental Biology (7940)
  • Ecology (12090)
  • Epidemiology (2067)
  • Evolutionary Biology (15971)
  • Genetics (10911)
  • Genomics (14721)
  • Immunology (9856)
  • Microbiology (23611)
  • Molecular Biology (9468)
  • Neuroscience (50791)
  • Paleontology (369)
  • Pathology (1537)
  • Pharmacology and Toxicology (2677)
  • Physiology (4004)
  • Plant Biology (8651)
  • Scientific Communication and Education (1507)
  • Synthetic Biology (2388)
  • Systems Biology (6419)
  • Zoology (1345)