细胞对溶酶体损伤的稳态反应。

Cellular homeostatic responses to lysosomal damage.

作者信息

Jia Jingyue, Poolsup Suttinee, Salinas Jay E

机构信息

Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87106, USA; Autophagy, Inflammation, and Metabolism Center of Biochemical Research Excellence, Albuquerque, NM 87106, USA.

出版信息

Trends Cell Biol. 2025 Mar 10. doi: 10.1016/j.tcb.2025.02.007.

DOI:10.1016/j.tcb.2025.02.007

PMID:40069045

Abstract

Lysosomes are essential membrane-bound organelles that control cellular homeostasis by integrating intracellular functions with external signals. Their critical roles make lysosomal membranes vulnerable to rupture under various stressors, leading to cellular dysfunction. However, the mechanisms by which cells respond to lysosomal damage have only recently begun to be explored. In this review, we summarize the cellular mechanisms activated by lysosomal damage, emphasizing those that restore lysosomal integrity and sustain homeostasis, including recognition, repair, removal, replacement, and remodeling. Drawing on our expertise, we provide an in-depth focus on the remodeling process involved in these responses, including metabolic signaling and stress granule formation. Finally, we discuss the implications of lysosomal damage in human diseases, underscoring potential therapeutic strategies to preserve lysosomal function and alleviate related disorders.

摘要

溶酶体是重要的膜结合细胞器，通过整合细胞内功能与外部信号来控制细胞内稳态。它们的关键作用使溶酶体膜在各种应激源作用下易破裂，导致细胞功能障碍。然而，细胞对溶酶体损伤的反应机制直到最近才开始被探索。在本综述中，我们总结了溶酶体损伤激活的细胞机制，重点强调那些恢复溶酶体完整性并维持内稳态的机制，包括识别、修复、清除、替换和重塑。凭借我们的专业知识，我们深入聚焦于这些反应中涉及的重塑过程，包括代谢信号传导和应激颗粒形成。最后，我们讨论溶酶体损伤在人类疾病中的意义，强调保护溶酶体功能和减轻相关疾病的潜在治疗策略。