bims-lycede 2024-08-18 papers

Autophagy. 2024 Aug 15.

Optogenetic manipulation of lysosomal physiology and autophagic activity.

Wenping Zeng, Canjun Li, Lili Qu, Chunlei Cang.

Lysosomes are essential degradative organelles and signaling hubs within cells, playing a crucial role in the regulation of macroautophagy/autophagy. Dysfunction of lysosomes and impaired autophagy are closely associated with the development of various neurodegenerative diseases. Enhancing lysosomal activity and boosting autophagy levels holds great promise as effective strategies for treating these diseases. However, there remains a lack of methods to dynamically regulate lysosomal activity and autophagy levels in living cells or animals. In our recent work, we applied optogenetics to manipulate lysosomal physiology and function, developing three lysosome-targeted optogenetic tools: lyso-NpHR3.0, lyso-ArchT, and lyso-ChR2. These new actuators enable light-dependent regulation of key aspects such as lysosomal membrane potential, lumenal pH, hydrolase activity, degradation processes, and Ca2+ dynamics in living cells. Notably, lyso-ChR2 activation induces autophagy via the MTOR pathway while it promotes Aβ clearance through autophagy induction in cellular models of Alzheimer disease. Furthermore, lyso-ChR2 activation reduces Aβ deposition and alleviates Aβ-induced paralysis in Caenorhabditis elegans models of Alzheimer disease. Our lysosomal optogenetic actuators offer a novel method for dynamically regulating lysosomal physiology and autophagic activity in living cells and animals.

Keywords: Alzheimer disease; MTOR; autophagy; lysosome; optogenetics

DOI: https://doi.org/10.1080/15548627.2024.2392464

J Cell Biol. 2024 Sep 02. pii: e202404152. [Epub ahead of print]223(9):

The endolysosomal system in conventional and unconventional protein secretion.

Eloïse Néel, Marioara Chiritoiu-Butnaru, William Fargues, Morgane Denus, Maëlle Colladant, Aurore Filaquier, Sarah E Stewart, Sylvain Lehmann, Chiara Zurzolo, David C Rubinsztein, Philippe Marin, Marie-Laure Parmentier, Julien Villeneuve.

Most secreted proteins are transported through the "conventional" endoplasmic reticulum-Golgi apparatus exocytic route for their delivery to the cell surface and release into the extracellular space. Nonetheless, formative discoveries have underscored the existence of alternative or "unconventional" secretory routes, which play a crucial role in exporting a diverse array of cytosolic proteins outside the cell in response to intrinsic demands, external cues, and environmental changes. In this context, lysosomes emerge as dynamic organelles positioned at the crossroads of multiple intracellular trafficking pathways, endowed with the capacity to fuse with the plasma membrane and recognized for their key role in both conventional and unconventional protein secretion. The recent recognition of lysosomal transport and exocytosis in the unconventional secretion of cargo proteins provides new and promising insights into our understanding of numerous physiological processes.

DOI: https://doi.org/10.1083/jcb.202404152

IET Nanobiotechnol. 2024 ;2024 3786627

Liposomal-Naringenin Radiosensitizes Triple-Negative Breast Cancer MDA-MB-231 Cells In Vitro.

Keenau Pearce, Samantha I Cairncross, Mongi Benjeddou.

Background: Naringenin has shown great promise in the realm of cancer therapeutics, demonstrating excellent cytotoxic action toward cancer cells and the enhanced effects of radiation therapy in vitro. However, the medicinal value of naringenin is severely limited clinically by poor bioavailability. Thus, multiple drug-delivery strategies for overcoming this limitation have been developed, of which liposomes are considered the most suitable due to their amphiphilic, modifiable, and biocompatible characteristics. In this study, we investigated the role of naringenin and liposomal-delivered naringenin as adjuncts to radiotherapy in the MDA-MB-231 triple-negative breast cancer cell line in vitro.
Materials and Methods: Liposomal-naringenin was synthesized by thin-film hydration and extrusion and was characterized by spectrophotometry, dynamic light scattering, and zeta potential. The effects of free-from naringenin and liposomal-naringenin were evaluated toward MDA-MB-231 cell viability when combined with varying doses of radiation. Additionally, cell growth patterns, morphology, and colony formation were evaluated.
Results: The analysis demonstrated IC50 values of 387.5 and 546.6 µg/ml for naringenin and liposomal-naringenin, respectively. Naringenin and liposomal-naringenin significantly lowered cell viability, proliferation, and colony formation dose-dependently, as compared to radiation in isolation.
Conclusion: The findings presented herein concur with previous accounts of the radiosensitizing potential of naringenin and further highlight the considerable biomedical application of liposomal-naringenin within the realm of radiotherapy.

DOI: https://doi.org/10.1049/2024/3786627