bims-lycede 2025-09-28 papers

Trends Biochem Sci. 2025 Sep 23. pii: S0968-0004(25)00218-X. [Epub ahead of print]

The interplay of the cGAS-STING pathway with the lysosome.

The cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon (IFN) genes (STING) pathway detects cytoplasmic DNA and elicits the innate immune response. Several recent studies show that cGAS-STING signaling not only terminates at the lysosome but also regulates lysosomal function. Here, we discuss the interplay of the cGAS-STING pathway with the lysosome.

Keywords: ESCRT; STING; TFEB; cGAS; innate immunity; lysosome

DOI: https://doi.org/10.1016/j.tibs.2025.08.010

Elife. 2025 Sep 24. pii: RP106901. [Epub ahead of print]14

Ubiquitination-activated TAB-TAK1-IKK-NF-κB axis modulates gene expression for cell survival in the lysosomal damage response.

Akinori Endo, Chikage Takahashi, Naoko Ishibashi, Yasumasa Nishito, Koji Yamano, Keiji Tanaka, Yukiko Yoshida.

The lysosomal damage response is important for the maintenance of cellular homeostasis in human cells. Although the mechanisms underlying the repair and autophagic elimination of damaged lysosomes have been elucidated, the early signal transduction pathways and genes induced in response to lysosomal damage remain elusive. We performed transcriptome and proteome analyses and found that the TAB-TAK1-IKK-NF-κB axis is activated by K63-linked ubiquitin chains that accumulate on damaged lysosomes. This activates the expression of various transcription factors and cytokines that promote anti-apoptosis and intercellular signaling. The findings highlight the crucial role of ubiquitin-regulated signal transduction and gene expression in cell survival and cell-cell communication in response to lysosomal damage. The results suggest that the ubiquitin system is not only involved in the removal of damaged lysosomes by lysophagy, but also functions in the activation of cellular signaling for cell survival.

Keywords: NF-κB; TAB; TAK1; cell biology; human; lysosomal damage response; ubiquitin

DOI: https://doi.org/10.7554/eLife.106901

J Zhejiang Univ Sci B. 2025 Aug 19. pii: 1673-1581(2025)09-0813-30. [Epub ahead of print]26(9): 813-842

Rescuing lysosomal/autophagic defects via nanoapproach: implications for lysosomal/autophagic defect-related diseases.

Xiaodan Huang, Yue Fang, Jie Song, Yuanjing Hao, Yuanyuan Cai, Pengfei Wei, Na Zhang.

The dysfunction of the lysosome and autophagy-lysosome system serves as a driving force for neurodegenerative diseases, metabolic disorders, inflammatory conditions, and other related diseases, closely influencing their onset and progression. Therefore, restoring the function of the lysosome or autophagy-lysosome system has become an increasingly crucial therapeutic strategy in disease management. In this review, we will introduce the lysosomal biogenesis, structure, and function, as well as the biological process of the autophagy-lysosome system. Various diseases closely associated with lysosomal/autophagic dysfunction are also reviewed, emphasizing the significance of targeting the function of the lysosome or autophagy-lysosome system in disease treatment. Finally, we focus on engineered nanomaterials that have the capabilities to restore the function of the lysosome or autophagy-lysosome system, and summarize different strategies and methods for achieving this goal. This review aims to elucidate the latest progress in the field of nanomedicine for lysosomal/autophagic defect-related diseases and inspire the development of innovative and clinically valuable nanomedicines.

Keywords: Acidic nanoparticle; Alzheimer’s disease; Autophagy; Dementia; Lysosomal/autophagic disfunction; Lysosome; Transcription factor EB (TFEB)

DOI: https://doi.org/10.1631/jzus.B2400186