Noncanonical functions of the autophagy machinery in pathways including LC3-associated phagocytosis and LC3-associated endocytosis have garnered increasing interest in both normal physiology and pathobiology. New discoveries over the past decade of noncanonical uses of the autophagy machinery in these distinct molecular mechanisms have led to robust investigation into the roles of single-membrane LC3 lipidation. Noncanonical autophagy pathways have now been implicated in the regulation of multiple processes ranging from debris clearance, cellular signaling, and immune regulation and inflammation. Accumulating evidence is demonstrating roles in a variety of disease states including host-pathogen responses, autoimmunity, cancer, and neurological and neurodegenerative pathologies. Here, we broadly summarize the differences in the mechanistic regulation between autophagy and LAP and LANDO and highlight some of the key roles of LAP and LANDO in innate immune function, inflammation, and disease pathology.
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http://dx.doi.org/10.1126/sciadv.abn1702 | DOI Listing |
Autophagy
December 2024
Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
(Mtb), the etiological agent of tuberculosis (TB), remains a significant global health challenge. Mtb is transmitted by respiratory aerosols and infects a variety of myeloid populations. Our recent study shows that the Mtb virulence lipid phthiocerol dimycocerosate (PDIM) promotes the intracellular survival of Mtb in macrophages by inhibiting NADPH oxidase, thereby impairing LC3-associated phagocytosis, and in vivo PDIM also antagonizes canonical macroautophagy/autophagy.
View Article and Find Full Text PDFNat Commun
November 2024
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, College of Life Sciences, Shandong Normal University, Jinan, 250358, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi
October 2024
Institute of Hematology, Xuzhou Medical University; Department of Hematology, Xuzhou Medical University Affiliated Hospital, Xuzhou 221002, Jiangsu Province, China.
Objective: To investigate the effects of and genes on the sensitivity of multiple myeloma (MM) cell line RPMI-8226 cells to ferroptosis.
Methods: CRISPR/Cas9 technology was used to knock out the autophagy key genes and in RPMI-8226 cells. Western blot was used to identify gene knockout cells, and detect the expression changes of autophagy-related proteins P62 and LC3B.
Front Immunol
October 2024
INSERM, EHESP, IRSET (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Univ Rennes, Rennes, France.
Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by antinuclear antibody production, which has been linked to an excess of apoptotic cells, normally eliminated by macrophages through efferocytosis. Additionally, circulating levels of CXCL4, a novel SSc biomarker, correlate with more severe fibrotic manifestations of the disease. Considering the defective efferocytosis of macrophages in SSc and the CXCL4-related M4 macrophage phenotype, we hypothesized that CXCL4 could be involved in the alteration of phagocytic functions of macrophages in SSc, including LC3-associated phagocytosis (LAP), another phagocytic process requiring autophagy proteins and contributing to immune silencing.
View Article and Find Full Text PDFFASEB J
October 2024
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China.
LC3-associated phagocytosis (LAP) is a distinct type of autophagy that involves the sequestration of extracellular material by phagocytes. Beyond the removal of dead cells and cellular debris from eukaryotic cells, LAP is also involved in the removal of a variety of pathogens, including bacteria, fungi, and viruses. These events are integral to multiple physiological and pathological processes, such as host defense, inflammation, and tissue homeostasis.
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