bims-lycede 2025-08-10 papers

Nat Rev Mol Cell Biol. 2025 Aug 04.

Lysosomal membrane homeostasis and its importance in physiology and disease.

Maja Radulovic, Chonglin Yang, Harald Stenmark.

Lysosomes are membranous organelles that are crucial for cell function and organ physiology. Serving as the terminal stations of the endocytic pathway, lysosomes have fundamental roles in the degradation of endogenous and exogenous macromolecules and particles as well as damaged or superfluous organelles. Moreover, the lysosomal membrane is a docking and activation platform for several signalling components, including mTOR complex 1 (mTORC1), which orchestrates metabolic signalling in the cell. The integrity of their membrane is crucial for lysosomes to function as hubs for the regulation of cell metabolism. Various agents, including pathogens, nanoparticles and drugs, can compromise lysosomal membrane integrity. Membrane permeabilization causes leakage of proteases and cations into the cytosol, which can induce cell death pathways and innate immunity signalling. Multiple pathways repair damaged lysosomes, and severely damaged lysosomes are degraded by an autophagic process, lysophagy. Moreover, lysosome damage activates transcriptional programmes that orchestrate lysosome biogenesis to replenish the cellular lysosome pool. In this Review, we discuss recent insights into the mechanisms that ensure the maintenance of lysosomal membrane homeostasis, including novel mechanisms of lysosomal membrane repair and the interplay between lysosome damage, repair, lysophagy and lysosome biogenesis. We highlight the importance of lysosomal membrane homeostasis in cell function, physiology, disease and ageing, and discuss the potential for therapeutic exploitation of lysosomal membrane permeabilization.

DOI: https://doi.org/10.1038/s41580-025-00873-w

NPJ Vaccines. 2025 Aug 05. 10(1): 184

Matrix-M adjuvant triggers inflammasome activation and enables antigen cross-presentation through induction of lysosomal membrane permeabilization.

Behdad Zarnegar, Berit Carow, Jens Eriksson, Eva Spennare, Pontus Öhlund, Eray Akpinar, Emelie Bringeland, Ingrid Lekberg Osterman, Lena Lundqvist, Johanna Antti, Niklas Handin, Per-Henrik Helgesson, Johan Bankefors, Karin Lövgren Bengtsson, Mikael E Sellin, Anna-Karin E Palm, Linda Stertman, Carolina Lunderius Andersson.

Matrix-M® adjuvant, containing saponins, delivers a potent adjuvant effect and good safety profile. Given that Matrix-M is composed of Matrix-A and Matrix-C particles, comprising different saponin fractions, understanding their distinct roles can provide deeper insight into the mechanism of action of Matrix-M and guide future applications. Here, we demonstrate that the antigen and Matrix-M, Matrix-A, or Matrix-C colocalize in lysosomes following uptake by bone marrow-derived dendritic cells. Matrix-M, Matrix-A, and Matrix-C induce lysosomal membrane permeabilization (LMP), but Matrix-C shows the highest LMP potential. LMP is required for interleukin (IL)-1β and IL-18 secretion in vitro. In vivo, a robust adjuvant effect of Matrix-M, Matrix-A, and Matrix-C is observed, both in the presence and absence of the NLRP3 inflammasome. LMP induced by Matrix-M, as well as Matrix-A and Matrix-C, also enables antigen cross-presentation. Thus, Matrix-induced LMP explains the capability of Matrix-M-adjuvanted protein vaccines to induce CD8+ T-cell responses.

DOI: https://doi.org/10.1038/s41541-025-01243-5

J Cell Mol Med. 2025 Aug;29(15): e70747

Naringenin Inhibits Cellular Proliferation, Arrests Cell Cycle and Induces Pro-Apoptotic Autophagy in MCF-7 Breast Cancer Cells.

Suhail Ahmad Mir, Basharat Ahmad Bhat, Priti S Shenoy, Laraibah Hamid, Nasir Nisar, Ashraf Dar, Pritha Ray, Ghulam Nabi Bader.

The global incidence of breast cancer has significantly increased, highlighting the need for novel therapeutic strategies. Current treatment options are often limited by drug resistance and adverse effects, necessitating the exploration of alternative compounds. Naringenin, a naturally occurring flavonoid in citrus fruits, exhibits antimicrobial, anti-atherogenic, hepatoprotective, anti-inflammatory, and anticancer properties. This study evaluates the potential of naringenin as an inhibitor of breast cancer cell proliferation. MCF-7 breast cancer cells were used as a model system to assess the anti-proliferative effects of naringenin. Cell viability was evaluated using MTT and colony formation assays, while cell migration was analysed via wound healing assay. Flow cytometry and western blotting were performed to examine cell cycle arrest and apoptosis, and autophagy was assessed through western blotting and confocal microscopy. Naringenin inhibited cellular proliferation in a dose-dependent manner by arresting cells in the S-phase of the cell cycle. It significantly reduced cellular migration and increased early and late apoptosis. Autophagy induction was confirmed by elevated LC3-II expression, p62 degradation, and LC3-II-LAMP1 co-localization. Additionally, C-PARP expression was reduced when cells were co-treated with naringenin and 3-methyladenine (3-MA), indicating pro-apoptotic autophagy. This study demonstrates the anti-migratory and anti-proliferative effects of naringenin and its ability to induce pro-apoptotic autophagy in human breast cancer cells, suggesting its potential as a therapeutic agent.

Keywords: apoptosis; autophagy; breast cancer; cell cycle; naringenin

DOI: https://doi.org/10.1111/jcmm.70747