Wang Quan, Wang Ruolin, Hu Haihui, Huo Xiaoqing, Wang Fulong
Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China.
Huaian Maternity and Child Healthcare Hospital of JiangSu Province, Huaian, China.
Front Cell Dev Biol. 2025 Mar 11;13:1559504. doi: 10.3389/fcell.2025.1559504. eCollection 2025.
Lysosomes are heterogeneous, acidic organelles whose proper functionality is critically dependent on maintaining the integrity of their membranes and the acidity within their lumen. When subjected to stress, the lysosomal membrane can become permeabilized, posing a significant risk to the organelle's survival and necessitating prompt repair. Although numerous mechanisms for lysosomal repair have been identified in recent years, the progression of lysosome-related diseases is more closely linked to the organelle's alternative strategies when repair mechanisms fail, particularly in the contexts of aging and pathogen infection. This review explores lysosomal responses to damage, including the secretion of lysosomal contents and the interactions with lysosome-associated organelles in the endolysosomal system. Furthermore, it examines the role of organelles outside this system, such as the endoplasmic reticulum (ER) and Golgi apparatus, as auxiliary organelles of the endolysosomal system. These alternative strategies are crucial to understanding disease progression. For instance, the secretion and spread of misfolded proteins play key roles in neurodegenerative disease advancement, while pathogen escape via lysosomal secretion and lysosomotropic drug expulsion underlie cancer treatment resistance. Reexamining these lysosomal fallback strategies could provide new perspectives on lysosomal biology and their contribution to disease progression.
溶酶体是异质性的酸性细胞器，其正常功能严重依赖于维持其膜的完整性及其腔内的酸性环境。在受到应激时，溶酶体膜可能会发生通透性改变，这对细胞器的存活构成重大风险，因此需要迅速修复。尽管近年来已发现多种溶酶体修复机制，但当修复机制失效时，尤其是在衰老和病原体感染的情况下，溶酶体相关疾病的进展与细胞器的替代策略更为密切相关。本综述探讨了溶酶体对损伤的反应，包括溶酶体内容物的分泌以及与内溶酶体系统中溶酶体相关细胞器的相互作用。此外，还研究了该系统之外的细胞器，如内质网（ER）和高尔基体，作为内溶酶体系统辅助细胞器的作用。这些替代策略对于理解疾病进展至关重要。例如，错误折叠蛋白的分泌和扩散在神经退行性疾病进展中起关键作用，而病原体通过溶酶体分泌逃逸和溶酶体亲和性药物排出是癌症治疗耐药性的基础。重新审视这些溶酶体的后备策略可为溶酶体生物学及其对疾病进展的贡献提供新的视角。
