Your browser doesn't support javascript.
loading
Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis.
Riley, Joel S; Quarato, Giovanni; Cloix, Catherine; Lopez, Jonathan; O'Prey, Jim; Pearson, Matthew; Chapman, James; Sesaki, Hiromi; Carlin, Leo M; Passos, João F; Wheeler, Ann P; Oberst, Andrew; Ryan, Kevin M; Tait, Stephen Wg.
Afiliación
  • Riley JS; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Quarato G; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Cloix C; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Lopez J; Cancer Research UK Beatson Institute, Glasgow, UK.
  • O'Prey J; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Pearson M; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Chapman J; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Sesaki H; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Carlin LM; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
  • Passos JF; MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, The University of Edinburgh, Edinburgh, UK.
  • Wheeler AP; Ageing Research Laboratories, Newcastle University Institute for Ageing, LLHW Centre for Ageing and Vitality, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, UK.
  • Oberst A; Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Ryan KM; Cancer Research UK Beatson Institute, Glasgow, UK.
  • Tait SW; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
EMBO J ; 37(17)2018 09 03.
Article en En | MEDLINE | ID: mdl-30049712
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 signalling. 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 signalling pathway. 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/BAK-mediated mitochondrial outer membrane pores gradually widen. 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 (MIMP) can occur during cell death following BAX/BAK-dependent MOMP Importantly, by enabling the cytosolic release of mtDNA, inner membrane permeabilisation underpins the immunogenic effects of caspase-independent cell death.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ADN Mitocondrial / Apoptosis / Membranas Mitocondriales / Mitocondrias Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2018 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ADN Mitocondrial / Apoptosis / Membranas Mitocondriales / Mitocondrias Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2018 Tipo del documento: Article