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Cytosolic Mycobacterium marinum are ejected from host cells such as macrophages or the amoeba Dictyostelium discoideum in a non-lytic fashion. As described previously, the autophagic machinery is recruited to ejecting bacteria and supports host cell integrity during egress. Here, we show that the ESCRT machinery is also recruited to ejecting bacteria, partially dependent on an intact autophagic pathway. As such, the AAA-ATPase Vps4 shows a distinct localization at the ejectosome structure in comparison to fluorescently tagged Vps32, Tsg101 and Alix. Along the bacterium engaged in ejection, ESCRT and the autophagic component Atg8 show partial colocalization. We hypothesize that both, the ESCRT and autophagic machinery localize to the bacterium as part of a membrane damage response, as well as part of a "frustrated autophagosome" that is unable to engulf the ejecting bacterium.
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http://dx.doi.org/10.1111/mmi.15075 | DOI Listing |
FEBS J
September 2025
Jiangsu Key Laboratory of Infection and Immunity, The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
Degradative autophagy supplies a source of nutrients and energy by digesting cytoplasmic components. Additionally, it eliminates toxic protein aggregates and defective organelles from cells. Exosomes are small vesicles that are released by cells into the extracellular environment and are also involved in maintenance of homeostasis by removing unwanted materials and intracellular pathogens.
View Article and Find Full Text PDFFront Immunol
August 2025
Center for Immunology and Inflammation, The Feinstein Institutes for Medical Research, Manhasset, NY, United States.
Macrophage extracellular traps (METs) are a poorly understood process beneficial for infection control but detrimental in inflammation, autoimmunity and cancer. Our research shows that viable macrophages release METs even when plasma membrane lysis is blocked. We demonstrate, for the first time, that nuclear DNA is extruded directly into the cytoplasm through Gasdermin D pores on the nuclear envelope.
View Article and Find Full Text PDFNat Commun
July 2025
Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences; MOE Key Laboratory & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
While ATG8ylation, the lipidation of ATG8-family proteins, is canonically linked to double-membrane autophagosome formation, emerging studies demonstrate its non-canonical association with single-membrane organelles. The functional significance of ATG8ylation in these compartments, however, remains unclear. Here, we demonstrate that ionophores rapidly trigger ATG8 conjugation to the vacuolar membrane (tonoplast), a process reliant on the ATG conjugation system rather than the upstream autophagic regulators.
View Article and Find Full Text PDFInt Rev Immunol
July 2025
Department of Biotechnology, School of Chemical and Life Sciences, New Delhi, India.
() employs diverse virulence factors to evade immune defenses and persist intracellularly. The ESAT-6 secretion system-1 (ESX-1) type VII secretion system (T7SS) releases EsxA, EspA, and EspB, inducing phagosomal rupture and cytosolic access while triggering host defenses, including galectin recruitment and stress granule formation. To counteract host responses, utilizes phthiocerol dimycocerosates (PDIMs) to inhibit autophagy and LC3-associated phagocytosis (LAP) by suppressing NADPH oxidase (NOX2) recruitment and reactive oxygen species (ROS) production.
View Article and Find Full Text PDFDev Cell
June 2025
Department of Genomic Medicine, University of Cambridge, Cambridge, UK; Cambridge Institute for Medical Research, Cambridge, UK; UK Dementia Research Institute, The Keith Peters Building Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK. Electronic address:
Autophagosome formation involves multiple sequential steps that need to be coordinated and linked. Here, we describe in mammalian cells that the transferrin receptor (TfR) links LC3 family conjugation to phagophore membranes, an early step in autophagosome biogenesis, with subsequent autophagosome closure. TfR depletion impairs autophagic flux and its overexpression stimulates this catabolic process in an iron-independent manner.
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