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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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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. |
format | Text |
id | pubmed-2996476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
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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