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Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria

IRGM, a human immunity related GTPase, confers autophagic defense against intracellular pathogens by an unknown mechanism. Here we report the unexpected mode of IRGM action. IRGM showed differential affinity for mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fi...

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Autores principales: Singh, Sudha B., Ornatowski, Wojciech, Vergne, Isabelle, Naylor, John, Delgado, Monica, Roberts, Esteban, Ponpuak, Marisa, Master, Sharon, Pilli, Manohar, White, Eileen, Komatsu, Masaaki, Deretic, Vojo
Formato: Texto
Lenguaje:English
Publicado: 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996476/
https://www.ncbi.nlm.nih.gov/pubmed/21102437
http://dx.doi.org/10.1038/ncb2119
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author Singh, Sudha B.
Ornatowski, Wojciech
Vergne, Isabelle
Naylor, John
Delgado, Monica
Roberts, Esteban
Ponpuak, Marisa
Master, Sharon
Pilli, Manohar
White, Eileen
Komatsu, Masaaki
Deretic, Vojo
author_facet Singh, Sudha B.
Ornatowski, Wojciech
Vergne, Isabelle
Naylor, John
Delgado, Monica
Roberts, Esteban
Ponpuak, Marisa
Master, Sharon
Pilli, Manohar
White, Eileen
Komatsu, Masaaki
Deretic, Vojo
author_sort Singh, Sudha B.
collection PubMed
description IRGM, a human immunity related GTPase, confers autophagic defense against intracellular pathogens by an unknown mechanism. Here we report the unexpected mode of IRGM action. IRGM showed differential affinity for mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fission and induced autophagy. Mitochondrial fission was necessary for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced mitochondrial membrane polarization and cell death. Overexpression of IRGMd but not IRGMb splice isoforms caused mitochondrial depolarization and autophagy-independent but Bax/Bak-dependent cell death. By acting on mitochondria IRGM confers autophagic protection or cell death, explaining IRGM action both in defense against tuberculosis and in damaging inflammation in Crohn's disease.
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spelling pubmed-29964762011-06-01 Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria Singh, Sudha B. Ornatowski, Wojciech Vergne, Isabelle Naylor, John Delgado, Monica Roberts, Esteban Ponpuak, Marisa Master, Sharon Pilli, Manohar White, Eileen Komatsu, Masaaki Deretic, Vojo Nat Cell Biol Article IRGM, a human immunity related GTPase, confers autophagic defense against intracellular pathogens by an unknown mechanism. Here we report the unexpected mode of IRGM action. IRGM showed differential affinity for mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fission and induced autophagy. Mitochondrial fission was necessary for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced mitochondrial membrane polarization and cell death. Overexpression of IRGMd but not IRGMb splice isoforms caused mitochondrial depolarization and autophagy-independent but Bax/Bak-dependent cell death. By acting on mitochondria IRGM confers autophagic protection or cell death, explaining IRGM action both in defense against tuberculosis and in damaging inflammation in Crohn's disease. 2010-11-21 2010-12 /pmc/articles/PMC2996476/ /pubmed/21102437 http://dx.doi.org/10.1038/ncb2119 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Singh, Sudha B.
Ornatowski, Wojciech
Vergne, Isabelle
Naylor, John
Delgado, Monica
Roberts, Esteban
Ponpuak, Marisa
Master, Sharon
Pilli, Manohar
White, Eileen
Komatsu, Masaaki
Deretic, Vojo
Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title_full Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title_fullStr Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title_full_unstemmed Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title_short Human IRGM Regulates Autophagy and Its Cell-Autonomous Immunity Functions Through Mitochondria
title_sort human irgm regulates autophagy and its cell-autonomous immunity functions through mitochondria
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996476/
https://www.ncbi.nlm.nih.gov/pubmed/21102437
http://dx.doi.org/10.1038/ncb2119
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