Department of Biochemistry, The Catholic University of Korea, Seoul, 06591, South Korea.
INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France.
Cell Death Dis. 2024 Jun 10;15(6):404. doi: 10.1038/s41419-024-06797-1.
Senescent cells exhibit a diverse spectrum of changes in their morphology, proliferative capacity, senescence-associated secretory phenotype (SASP) production, and mitochondrial homeostasis. These cells often manifest with elongated mitochondria, a hallmark of cellular senescence. However, the precise regulatory mechanisms orchestrating this phenomenon remain predominantly unexplored. In this study, we provide compelling evidence for decreases in TIA-1, a pivotal regulator of mitochondrial dynamics, in models of both replicative senescence and ionizing radiation (IR)-induced senescence. The downregulation of TIA-1 was determined to trigger mitochondrial elongation and enhance the expression of senescence-associated β-galactosidase, a marker of cellular senescence, in human foreskin fibroblast HS27 cells and human keratinocyte HaCaT cells. Conversely, the overexpression of TIA-1 mitigated IR-induced cellular senescence. Notably, we identified the miR-30-5p family as a novel factor regulating TIA-1 expression. Augmented expression of the miR-30-5p family was responsible for driving mitochondrial elongation and promoting cellular senescence in response to IR. Taken together, our findings underscore the significance of the miR-30-5p/TIA-1 axis in governing mitochondrial dynamics and cellular senescence.
衰老细胞在形态、增殖能力、衰老相关分泌表型（SASP）产生和线粒体稳态方面表现出多样化的变化。这些细胞通常表现出线粒体伸长，这是细胞衰老的一个标志。然而，协调这一现象的确切调节机制在很大程度上仍未得到探索。在这项研究中，我们提供了令人信服的证据，表明在复制性衰老和电离辐射（IR）诱导的衰老模型中，线粒体动态的关键调节因子 TIA-1 减少。下调 TIA-1 被确定会触发线粒体伸长，并增强人包皮成纤维细胞 HS27 细胞和人角质形成细胞 HaCaT 细胞中衰老相关β-半乳糖苷酶的表达，这是细胞衰老的一个标志物。相反，TIA-1 的过表达减轻了 IR 诱导的细胞衰老。值得注意的是，我们确定了 miR-30-5p 家族是调节 TIA-1 表达的一个新因素。miR-30-5p 家族的表达增加导致线粒体伸长，并响应 IR 促进细胞衰老。总之，我们的研究结果强调了 miR-30-5p/TIA-1 轴在调节线粒体动力学和细胞衰老中的重要性。
