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

Activated BAX/BAK enable mitochondrial inner membrane permeabilisation and mtDNA release during cell death

Joel Riley, Giovanni Quarato, Jonathan Lopez, Jim O'Prey, Matthew Pearson, James Chapman, Hiromi Sesaki, Leo Carlin, Joao Passos, Ann Wheeler, Andrew Oberst, Kevin Ryan, View ORCID ProfileStephen Tait
doi: https://doi.org/10.1101/272104
Joel Riley
Beatson Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giovanni Quarato
St Jude Children's Hospital;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan Lopez
Beatson Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jim O'Prey
Beaston Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew Pearson
University of Edinburgh;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Chapman
University of Newcastle;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiromi Sesaki
Johns Hopkins University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Leo Carlin
Beaston Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joao Passos
University of Newcastle;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ann Wheeler
University of Edinburgh;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew Oberst
Washington University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin Ryan
Beatson Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen Tait
Beatson Institute;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Stephen Tait
  • For correspondence: stephen.tait@glasgow.ac.uk
  • Abstract
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

During apoptosis, pro-apoptotic BAX and BAK are activated, causing mitochondrial outer membrane permeabilisation (MOMP), caspase activation and cell death. However, even in the absence of caspase activity, cells usually die following MOMP. Such caspase-independent cell death is accompanied by inflammation that requires mitochondrial DNA (mtDNA) activation of cGAS-STING signaling. Because the mitochondrial inner membrane is thought to remain intact during apoptosis, we sought to address how matrix mtDNA could activate the cytosolic cGAS-STING signaling pathway. Strikingly, using super-resolution imaging, we show that mtDNA is efficiently released from mitochondria following MOMP. In a temporal manner, we find that following MOMP, BAX/BAKmediated mitochondrial outer membrane pores gradually widen over time. This allows extrusion of the mitochondrial inner membrane into the cytosol whereupon it permeablises allowing mtDNA release. Our data demonstrate that mitochondrial inner membrane permeabilisation can occur during cell death in a BAX/BAK-dependent manner. Importantly, by enabling the cytosolic release of mtDNA, inner membrane permeabilisation underpins the immunogenic effects of caspase independent cell death.

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 February 26, 2018.
Download PDF

Supplementary Material

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.
Activated BAX/BAK enable mitochondrial inner membrane permeabilisation and mtDNA release during cell death
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Activated BAX/BAK enable mitochondrial inner membrane permeabilisation and mtDNA release during cell death
Joel Riley, Giovanni Quarato, Jonathan Lopez, Jim O'Prey, Matthew Pearson, James Chapman, Hiromi Sesaki, Leo Carlin, Joao Passos, Ann Wheeler, Andrew Oberst, Kevin Ryan, Stephen Tait
bioRxiv 272104; doi: https://doi.org/10.1101/272104
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Activated BAX/BAK enable mitochondrial inner membrane permeabilisation and mtDNA release during cell death
Joel Riley, Giovanni Quarato, Jonathan Lopez, Jim O'Prey, Matthew Pearson, James Chapman, Hiromi Sesaki, Leo Carlin, Joao Passos, Ann Wheeler, Andrew Oberst, Kevin Ryan, Stephen Tait
bioRxiv 272104; doi: https://doi.org/10.1101/272104

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

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (996)
  • Biochemistry (1485)
  • Bioengineering (938)
  • Bioinformatics (6803)
  • Biophysics (2414)
  • Cancer Biology (1782)
  • Cell Biology (2514)
  • Clinical Trials (106)
  • Developmental Biology (1683)
  • Ecology (2553)
  • Epidemiology (1488)
  • Evolutionary Biology (5003)
  • Genetics (3598)
  • Genomics (4614)
  • Immunology (1157)
  • Microbiology (4222)
  • Molecular Biology (1617)
  • Neuroscience (10744)
  • Paleontology (81)
  • Pathology (236)
  • Pharmacology and Toxicology (407)
  • Physiology (552)
  • Plant Biology (1445)
  • Scientific Communication and Education (410)
  • Synthetic Biology (542)
  • Systems Biology (1868)
  • Zoology (257)