Selective autophagy gets more selective: Uncoupling of autophagy flux and xenophagy flux in Mycobacterium tuberculosis-infected macrophages. Issue 3 (3rd March 2016)

• Record Type: Journal Article
• Authors: Chandra, Pallavi; Kumar, Dhiraj
• Is Part Of: Autophagy. Volume 12:Issue 3(2016)
• Page Start: 608
• Page End: 609
• Publication Date: 2016-03-03
• Subjects: amphisomes -- autophagy flux -- LC3 -- Mycobacterium tuberculosis -- macrophages -- RAB7 -- xenophagy; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2016.1139263
• Languages: English
• ISSNs: 1554-8627

Abstract

Abstract: Induction of autophagy has been reported as a potential means to eliminate intracellular pathogens. Corroborating that, many studies report inhibition of autophagy as a survival strategy of bacterial pathogens. Incidentally, autophagy at the basal level is critical for survival of host cells including macrophages. We asked how a bacterial pathogen could inhibit autophagy for its survival if the inhibition resulted in cell death. In a recent study we show distinct regulation of autophagy in Mycobacterium tuberculosis ( Mtb )-infected macrophages where Mtb containing- and non Mtb -containing autophagosomes show different fates in terms of maturation. We show that upon Mtb infection, there is no dramatic change in the autophagy flux in macrophages. However, autophagosomes that contain the virulent strains of Mtb show selective resilience to the maturation phase of autophagy. Surprisingly, non Mtb -containing autophagosomes in the infected cells continue to mature into autolysosomes. The block in the xenophagy flux is missing in the case of avirulant infections. We show that this selectivity is achieved through selective exclusion of RAB7 from virulent Mtb -containing autophagosomes, thereby restricting the formation of amphisomes.