Molecular mechanism of interferon-gamma-induced-autophagy

What is it about?

This manuscript describes the molecular mechanism of the interferon gamma induced autophagy. Interferon gamma induced autophagy plays a critical role in clearance of several pathogens including Mycobacterium, the causative agent of Tuberculosis. This study demonstrates that exposure of macrophages to interferon gamma leads to increased intracellular calcium levels in a heme oxygenase-1 dependent manner. Heme oxygenase is a stress responsive and cytoprotective enzyme. The increased calcium levels then induces the phosphatase calcineurin to dephosphorylate transcription factor EB (TFEB). TFEB is a master regulator of autophagy. The phosphorylated form of TFEB localizes in the cytoplasm, while the dephosphorylated form resides in the nucleus. Once inside the nucleus, TFEB induces transcription of genes encoding for lysosomal biogenesis and autophagy. In this manner, interferon gamma induced autophagy in macrophage cells to eliminate the pathogens such as Mycobacterium tuberculosis.

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Why is it important?

This study is important as it unravels the signalling cascade the govern the induction of autophagy by interferon gamma.

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