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LAPTM5 Confers the Resistance to Venetoclax via Promoting the Autophagosome-Lysosome Fusion in Multiple Myeloma.
J Cell Mol Med
January 2025
School of Life Sciences, Anhui Medical University, Hefei, China.
Multiple myeloma (MM) is a haematological lymphoid malignancy marked by significant morbidity due to severe complications. Despite advances in targeted therapies, including proteasome inhibitors and the BCL-2 inhibitor venetoclax, drug resistance frequently occurs, with the underlying mechanisms poorly understood. This study investigates the role of lysosome-associated protein transmembrane 5 (LAPTM5) in conferring resistance to venetoclax in relapsed MM.
View Article and Find Full Text PDFDynamic interplay of autophagy and membrane repair during Mycobacterium tuberculosis Infection.
PLoS Pathog
January 2025
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland United States of America.
Autophagy plays a crucial role in the host response to Mycobacterium tuberculosis (Mtb) infection, yet the dynamics and regulation of autophagy induction on Mtb-containing vacuoles (MCVs) remain only partially understood. We employed time-lapse confocal microscopy to investigate the recruitment of LC3B (LC3), a key autophagy marker, to MCVs at the single cell level with our newly developed workflow for single cell and single MCV tracking and fluorescence quantification. We show that approximately 70% of MCVs exhibited LC3 recruitment but that was lost in about 40% of those MCVs.
View Article and Find Full Text PDFATG9A facilitates the closure of mammalian autophagosomes.
J Cell Biol
February 2025
Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite for its subsequent fusion with endolysosomal organelles and degradation of the sequestered cargo. ATG9A, a key integral membrane protein of the autophagy pathway, is best known for its role in the formation and expansion of phagophores.
View Article and Find Full Text PDFAsparagine endopeptidase regulates lysosome homeostasis via modulating endomembrane phosphoinositide composition.
Cell Death Dis
January 2025
College of Pharmacy, Dali University, Dali 671003, Yunnan, PR China.
Asparagine endopeptidase (AEP) is ubiquitously expressed in both physiological and pathological contexts, yet its precise role and functional mechanism in breast cancer remain elusive. Here, we identified increased AEP expression in breast cancer tissues, which correlated with poorer survival rates and a propensity for lung metastasis among breast cancer patients. Loss of AEP impaired colony formation by breast cancer cells in vitro and suppressed lung metastasis in mice.
View Article and Find Full Text PDFDe Novo Design of Lipopeptide-Based β-Sheet-Like Self-Assemblies: A Strategy to Develop Fusion Inhibitors as Broad-Spectrum Antivirals.
Chemistry
December 2024
"Indian Institute of Science Education and Research Kolkata", Chemical Sciences, Research Complex, 741246, Mohanpur, INDIA.
The recent surge in emerging viral infections warrants the design of broad-spectrum antivirals. We aim to develop a lead molecule that targets a common biochemical feature of many enveloped viruses, membrane fusion. To achieve the broad-spectrum ability, instead of targeting the fusion machinery, we plan to modulate the physicochemical properties of the host and viral membranes to block fusion.
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