bims-lypmec 2026-03-15 papers

J Cell Biol. 2026 May 04. pii: e202509180. [Epub ahead of print]225(5):

Mechanoresilience of lysosomes conferred by TMEM63A.

Angelina S Kim, Jing Ze Wu, Ruiqi Cai, Spencer A Freeman.

Lysosomes are subject to perturbations that can cause damage to their limiting membrane. Osmotic shifts, pore-forming toxins, and the growth of luminal polymers or pathogens all stand to increase lysosomal membrane tension and/or disrupt the bilayer. In some contexts, this leads to lysosomal rupture and cell death. Here, we describe a mechanism that enables lysosomes to sense and respond to acute increases in tension of their limiting membrane. We report that the lysosome-resident nonselective cation channel, TMEM63A, can drive the directional flux of monovalent cations, major osmoticants, out of the lumen when gated by mechanical tension on the organelle. This results in the ability for lysosomes to relieve hydrostatic pressure and, proportionally, membrane tension, affording lysosomes the time to acquire additional lipids. Lysosomes without this mechanism-either because TMEM63A is deleted or in the case when cells express disease-causing variants of TMEM63A-are an order of magnitude more sensitive to lysis upon increases to their membrane tension when compared with their WT counterparts. These findings suggest that lysosomes are capable of regulating hydrostatic pressure and volume in response to high tension.

DOI: https://doi.org/10.1083/jcb.202509180

Trends Cancer. 2026 Mar 11. pii: S2405-8033(26)00025-7. [Epub ahead of print]

A lysosomal requiem for glioblastoma cells.

Laura Merlet, Margaux Le Guyon, Julie Gavard.

Once viewed solely as degradative compartments, lysosomes shape cell fate through signaling, metabolism, and communication. In glioblastoma, their rewiring underlies plasticity, invasion, and resistance to therapies. This forum explores lysosomal dynamics in brain tumors and therapeutic strategies targeting lysosomal vulnerabilities, offering fresh perspectives for precision approaches in this lethal cancer.

Keywords: autophagy; cell death; endolysosome; glioma; organelles

DOI: https://doi.org/10.1016/j.trecan.2026.01.012

Cardiovasc Diabetol. 2026 Mar 07.

Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.

Yan Liu, Hongshuo Shi, Chun Li, Haowen Zhuang, Yinglong Li, Xiuling He, Ying Jiang, Zhiyu Jin, Zhijiang Guo, Sangbing Ong, Yuanyuan Wang, Xing Chang, Guipeng An, Junyan Wang.

BACKGROUND: Diabetic cardiomyopathy (DCM) involves cardiac dysfunction/remodeling with mitochondrial stress and impaired mitochondrial proteostasis. The role of dual-specificity phosphatases (DUSPs) in these processes remains unclear. We examined whether Dusp15 modulates diabetic cardiac injury and whether mtHsp70/mito-UPR-linked proteostasis is involved.
METHODS: DCM was induced in mice by high-fat diet (HFD) combined with low-dose streptozotocin (STZ). We studied cardiomyocyte-specific Dusp15 knockout (Dusp15Cko) mice, a Dusp15 gain-of-function line, and high-glucose-treated HL-1 cardiomyocytes. Cardiac function/remodeling were assessed by echocardiography and molecular/histological analyses. Dusp15-mtHsp70 signaling was interrogated by protein interaction assays and mtHsp70 Thr116 genetic models.
RESULTS: Dusp15 was reduced in diabetic hearts and associated with impaired contractility. Dusp15 gain-of-function improved cardiac function and reduced remodeling/inflammation, whereas Dusp15Cko worsened diabetic injury, indicating a cardiomyocyte-necessary role for Dusp15. Dusp15 associated with mtHsp70 and supported mtHsp70-linked mitochondrial proteostasis/mito-UPR in cardiomyocytes. Genetically, mtHsp70T116A knock-in mice were substantially protected from diabetic cardiac dysfunction/remodeling. Finally, dapagliflozin (DAPA) improved diabetic cardiac outcomes, and its benefit was reduced in Dusp15Cko mice, suggesting Dusp15 as an important mediator.
CONCLUSION: Dusp15 is a stress-responsive regulator that protects against diabetic cardiac dysfunction and remodeling through mtHsp70-associated mito-UPR signaling. Targeting the Dusp15-mtHsp70 axis may represent a therapeutic strategy for diabetic cardiomyopathy.

Keywords: Diabetic cardiomyopathy; Dusp15; Mitochondrial unfolded protein response; mtHsp70

DOI: https://doi.org/10.1186/s12933-026-03125-z

Molecules. 2026 Feb 25. pii: 763. [Epub ahead of print]31(5):

New Insights into the Anti-Aging Mechanism of Collagen Peptides-Emphasis on Lysosomes and Mitochondria Function.

Wei Huang, Jinshan Ran, Yanli Du, Changwei Cao.

With the intensification of social aging and the improvement of living standards, delaying aging has become a focus of common concern, especially in regard to skin aging. Although collagen peptides have been widely reported as therapeutic agents in relieving skin aging, the molecular mechanisms remain inadequately elucidated. This review emphasizes that the alleviation of skin aging by collagen peptides is a systematic and complex process, including the removal of reactive oxygen species, inhibition of inflammation, inhibition of extracellular matrix (ECM) degradation and melanin deposition, activation of lysosomal and mitochondrial function, and promotion of ECM synthesis. It also highlights that lysosomes and mitochondria may be the key organelles that regulate collagen peptides to alleviate skin aging. Current research on the mechanism of collagen peptides in alleviating skin aging still requires bold breakthroughs and should not be confined to the transforming growth factor (TGF-β)/Smad, mitogen-activated protein kinase, and nuclear factor kappa-B pathways. In addition, many natural antioxidant components have been proven to alleviate skin aging by regulating organelle function. Therefore, the regulatory effects of collagen peptides with antioxidant activity on mitochondrial and lysosome functions in aging skin need more attention and exploration, which is of great significance for further research on precise skin care and targeted anti-skin aging therapy.

Keywords: collagen peptides; lysosomes; mitochondria; precise anti-aging; skin aging

DOI: https://doi.org/10.3390/molecules31050763