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Title: Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria
Authors: 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
University of New Mexico Health Sciences Center
Mahidol University
The Cancer Institute of New Jersey
Tokyo Metropolitan Institute of Medical Science
Juntendo University School of Medicine
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Dec-2010
Citation: Nature Cell Biology. Vol.12, No.12 (2010), 1154-1165
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.
ISSN: 14657392
Appears in Collections:Scopus 2006-2010

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