Lysosome remodelling and adaptation during phagocyte activation

Abstract
Lysosomes are acidic and hydrolytic organelles responsible for receiving and digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For macrophages and dendritic cells, the lysosome is kingpin, playing a direct role in microbe killing and antigen processing for presentation. Strikingly, the historic view that lysosomes are homogeneous and static organelles is being replaced with a more elegant paradigm, in which lysosomes are heterogeneous, dynamic and respond to cellular needs. For example, lysosomes are signaling platforms that integrate stress detection and molecular decision hubs like mTORC1 and AMPK to modulate cellular activity. These signals can even adjust lysosome activity by modulating transcription factors like TFEB and TFE3 that govern lysosome gene expression. Here, we review lysosome remodeling and adaptation during macrophage and dendritic cell stimulation. First, we assess the functional outcomes and regulatory mechanisms driving the dramatic restructuring of lysosomes from globular organelles into a tubular network during phagocyte activation. Second, we discuss lysosome adaptation and scaling in macrophages driven by TFEB and TFE3 stimulation in response to phagocytosis and microbe challenges. Collectively, we are beginning to appreciate that lysosomes are dynamic and adapt to serve phagocyte differentiation in response to microbes and immune stress.

Source: Cellular Microbiology - January 19, 2018 Category: Microbiology Authors: Victoria E.B. Hipolito, Erika Ospina ‐Escobar, Roberto J. Botelho Tags: MICROREVIEW Source Type: research