近日，
研究人员报告了功能障碍的线粒体质量控制通过逆行（线粒体-核）信号通路，损害β细胞、肝细胞和棕色脂肪细胞的细胞特征和成熟度。
在整个线粒体质量控制路径中，包括基因组完整性、动态变化或更替的靶向缺失，损害了氧化磷酸化机制，激活了线粒体综合应激反应，引发了染色质重塑，并促进了细胞的不成熟而非凋亡，导致代谢功能紊乱。
事实上，在体内药物阻断综合应激反应后，恢复了β细胞在失去线粒体质量控制后的身份。因此，靶向线粒体逆行信号可能在代谢疾病的治疗或预防中具有潜力。
据介绍，线粒体损伤是代谢性疾病（包括糖尿病）的一个标志，但线粒体功能受损在代谢组织中的后果通常不明确。
附：英文原文
Title: Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues
Author: Emily M. Walker, Gemma L. Pearson, Nathan Lawlor, Ava M. Stendahl, Anne Lietzke, Vaibhav Sidarala, Jie Zhu, Tracy Stromer, Emma C. Reck, Jin Li, Elena Levi-D’Ancona, Mabelle B. Pasmooij, Dre L. Hubers, Aaron Renberg, Kawthar Mohamed, Vishal S. Parekh, Irina X. Zhang, Benjamin Thompson, Deqiang Zhang, Sarah A. Ware, Leena Haataja, Nathan Qi, Stephen C. J. Parker, Peter Arvan, Lei Yin, Brett A. Kaufman, Leslie S. Satin, Lori Sussel, Michael L. Stitzel, Scott A. Soleimanpour
Issue&Volume: 2025-02-06
Abstract: Mitochondrial damage is a hallmark of metabolic diseases, including diabetes, yet the consequences of compromised mitochondria in metabolic tissues are often unclear. Here, we report that dysfunctional mitochondrial quality control engages a retrograde (mitonuclear) signaling program that impairs cellular identity and maturity in β-cells, hepatocytes, and brown adipocytes. Targeted deficiency throughout the mitochondrial quality control pathway, including genome integrity, dynamics, or turnover, impaired the oxidative phosphorylation machinery, activating the mitochondrial integrated stress response, eliciting chromatin remodeling, and promoting cellular immaturity rather than apoptosis to yield metabolic dysfunction. Indeed, pharmacologic blockade of the integrated stress response in vivo restored β-cell identity following loss of mitochondrial quality control. Targeting mitochondrial retrograde signaling may therefore be promising in the treatment or prevention of metabolic disorders.
DOI: adf2034
Source: https://www.science.org/doi/10.1126/science.adf2034