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- Title
Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria.
- Authors
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
- 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.
- Subjects
GUANOSINE triphosphatase; IMMUNITY; MITOCHONDRIA; CARDIOLIPIN; TUBERCULOSIS; CROHN'S disease
- Publication
Nature Cell Biology, 2010, Vol 12, Issue 12, p1154
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb2119