Human IRGM Regulates Autophagy and Cell-autonomous Immunity Functions Through Mitochondria

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2010 Nov 25

PMID 21102437

Citations 145

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

Affiliations

Soon will be listed here.

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.

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