Publication: Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria
Issued Date
2010-12-01
Resource Type
ISSN
14657392
DOI
Other identifier(s)
2-s2.0-78649833818
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Cell Biology. Vol.12, No.12 (2010), 1154-1165
Suggested Citation
Sudha B. Singh, Wojciech Ornatowski, Isabelle Vergne, John Naylor, Monica Delgado, Esteban Roberts, Marisa Ponpuak, Sharon Master, Manohar Pilli, Eileen White, Masaaki Komatsu, Vojo Deretic Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nature Cell Biology. Vol.12, No.12 (2010), 1154-1165. doi:10.1038/ncb2119 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/28590
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Title
Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria
Abstract
IRGM, a human immunity-related GTPase, confers autophagic defence against intracellular pathogens by an unknown mechanism. Here, we report an unexpected mode of IRGM action. IRGM demonstrated differential affinity for the 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 defence against tuberculosis and in the damaging inflammation caused by Crohn's disease. © 2010 Macmillan Publishers Limited. All rights reserved.