bims-lypmec 2026-04-12 papers

Ageing Res Rev. 2026 Apr 08. pii: S1568-1637(26)00126-1. [Epub ahead of print] 103134

Lysosomal Control of Aging through Transcriptional and Epigenetic Regulation.

Yikai Bai, Yu Luo, Yuyuan Wang, Jiayi Qiu, Dan Li.

Despite the well-known role as degradative organelles, lysosomes have been identified as a central signaling hub in maintaining cellular homeostasis. Lysosomal dysfunction is a well-established driver of cellular senescence and age-related pathologies. However, the precise molecular mechanisms through which lysosomes actively regulate aging remain unclear. Excitingly, latest studies show that lysosomes are not merely passive in aging but may actively govern longevity. In this review we summarize two significant discoveries about lysosome and senescence. Li et al. discovered the lysosomal surveillance response (LySR) and Zhang et al. uncovered transgenerational lysosomal signaling. These pathways substantially contribute to enhanced organismal longevity. We further discuss the transcription factor EB (TFEB) as a central regulator linking lysosomal activity to senescence and tissue homeostasis. Together, these findings reposition lysosomes as dynamic regulators that integrate stress and metabolic cues to modulate aging programs. Therefore, targeting lysosomal signaling emerges as a promising strategy for extending healthspan and mitigating age-related disorders.

Keywords: Aging; Lysosome; Senescence; Transcription, TFEB

DOI: https://doi.org/10.1016/j.arr.2026.103134

Cell Mol Biol Lett. 2026 Apr 09.

Restoration of lysosomal membrane integrity in cell models of Pompe disease depends on fatty acid synthase and its product palmitic acid.

Edouard Le Guillou, Arianna Segaloni, Alexis Gadault, Catia Oliveira Dias, Nathaniel F Henneman, Min Su, Ivan Nemazanyy, Nesrine Hifdi, Valérie Nivet-Antoine, Michael Laemmerhofer, Karim Hnia, Catherine Caillaud, Ganna Panasyuk.

Keywords: Class 3 PI3K; Fatty acid synthase; Lysosomal membrane damage; Lysosomal storage disorders; Lysosome; Palmitic acid; Pompe disease

DOI: https://doi.org/10.1186/s11658-026-00897-w

FASEB J. 2026 Apr 30. 40(8): e71717

Lysosomal Membrane Proteins: Key Regulators of Glucose Metabolism and Its Associated Diseases.

Jiahao Xu, Yujie Jin, Shiqiang Liu, Song Dong, Chaoqun Xiong, Ruixi Zhang, Wenjun Pei, Xu Wu, Lizhuo Wang, Jialin Gao.

Glucose homeostasis, which is critical for maintaining energy supply and health, involves glycogen metabolism, glycolysis, and gluconeogenesis. Lysosomal membrane proteins (LMPs) play core roles in regulating these processes. However, no focused systematic review of the topic has been reported. This review provides an in-depth analysis of the central roles of LMPs in glucose metabolism, focusing on the regulation of glucose homeostasis and their potential effects on metabolic diseases through the regulation of autophagy, signaling networks, specialized transporter functions, and other relevant mechanisms. In general, LMPs play core roles in lysosomal biosynthesis, and an in-depth study of their relationship with glucose metabolism could significantly highlight the important contribution of lysosomes in the development of related diseases.

Keywords: gene regulation; glucose metabolism; lysosomal membrane protein; metabolism; molecular mechanisms

DOI: https://doi.org/10.1096/fj.202501587R

Dev Cell. 2026 Apr 08. pii: S1534-5807(26)00086-9. [Epub ahead of print]61(4): 709-710

Lysosomal rupture: An emerging switch for collective ferroptosis.

Wenxin Zhang, Junren Dai, Ying Hu.

Ferroptosis can propagate collectively between cells. In this issue of Developmental Cell, Das et al.1 report that glutathione (GSH) depletion converts glutathione peroxidase 4 (GPX4)-inhibition-induced ferroptosis from a single-cell to a collective fate, and confirms the central role of lysosomal rupture in this process.

DOI: https://doi.org/10.1016/j.devcel.2026.03.002

Genes Dis. 2026 Jul;13(4): 101936

Crosstalk between autophagy and ferroptosis in diabetes.

Erlian Xie, Xuerong Wei, Zijun Zheng, Qiuyi Yu, Mengqian Liu, Huihui Zhang, Ziwei Jiang, Yanbin Gao, Lei Yang.

Diabetes is a multifactorial metabolic disease involving complex disruptions in cellular homeostasis and multiple forms of regulated cell death. Among them, the interaction between autophagy and ferroptosis has recently gained increasing attention. Autophagy is a catabolic process essential for degrading damaged organelles and misfolded proteins, thus preserving cellular integrity. Ferroptosis, on the other hand, is a newly identified, iron-dependent form of cell death characterized by excessive lipid peroxidation. Emerging evidence suggests that these two processes are intricately linked through shared regulatory pathways involving iron metabolism, lipid homeostasis, and the antioxidant system. Their crosstalk plays crucial roles in key diabetic pathologies, including pancreatic β-cell dysfunction, insulin resistance, and vascular complications. This review provides a comprehensive overview of the molecular mechanisms underlying autophagy-ferroptosis interactions in diabetes and highlights how their cooperative or antagonistic actions contribute to disease progression. Additionally, we discuss novel therapeutic strategies aimed at modulating this interplay, which may offer promising avenues for improving outcomes in diabetes and its complications. Further studies are needed to define precise molecular targets and facilitate clinical translation.

Keywords: Autophagy; Co-mechanism; Diabetes mellitus; Diabetic complications; Ferroptosis

DOI: https://doi.org/10.1016/j.gendis.2025.101936

Cell Death Dis. 2026 Apr 04.

Organelle contact sites in cancer cells.

Ilaria Celotti, Matteo Scavezzon, Sabrina Toffanin, Alessia Ruzza, Federica Vianello, Elisabetta Zaltron, Carol Bastianello, Michela Rossini, Filippo Severin, Luigi Leanza.

Membrane contact sites (MCSs) are defined as regions of functional proximity between membranes belonging to the same or different organelle types. These interactions are mediated by specialised proteins promoting the formation of these crosstalk hubs. Previously, organelles were considered to act independently in cellular physiology. However, it is now evident they carry out specific functions at MCSs. The first interactions described involved endoplasmic reticulum and mitochondria. Subsequently, many contacts involving different organelles emerged. MCSs affect several cellular processes, including intracellular signalling, lipid and ion homeostasis, transport of molecules, cellular metabolism, and redox balance. Disruption of these interactions has been described to be associated with various pathologies, including cancer. While the role of MCSs in tumours remains unclear, recent findings suggest they may influence cancer progression, so, in the near future, modulating organelle interactions could provide novel therapeutic options and develop new protocol to treat tumours.Schematic overview of intracellular MCSs, their effects on biological processes and the associated cancer-related outcomes. MCSs involve different cellular organelles allowing their intercommunication, finally participating in a plethora of cellular processes ranking from calcium and ions exchange, lipid transport and regulation of cell survival. Thus, MCSs modulation has been demonstrated to play a pivotal role in the modulation of cancer aggressiveness.

DOI: https://doi.org/10.1038/s41419-026-08674-5