意大利帕多瓦大学Sirio Dupont团队近期取得重要工作进展，他们研究提出，线粒体机械传导通过MIEF1协调核对力的反应。相关研究成果2024年10月21日在线发表于《自然—细胞生物学》杂志上。

据介绍，组织尺度结构和力学特性指导细胞在生理和疾病条件下的行为，但人们对潜在机制的理解仍然是零碎的。

研究人员表明细胞外基质刚度、空间限制和施加的力，包括小鼠皮肤的拉伸，调节线粒体动力学。肌动球蛋白张力促进线粒体延长因子1（MIEF1）的磷酸化，限制线粒体上动力蛋白相关蛋白1（DRP1）的募集，以及线粒体周围F-actin的形成和线粒体分裂。线粒体分裂也是一种普遍的机械转导机制。

研究人员发现DRP1和MIEF1/2依赖性分裂是必需的，足以调节三种广泛相关的转录因子（YAP/TAZ、SREBP1/2和NRF2），以控制细胞增殖、脂肪生成、抗氧化代谢、化疗耐药性和脂肪细胞分化，来响应机械信号。这延伸到了小鼠肝脏，DRP1在肝脏中调节肝细胞增殖和依赖 YAP 的特征表型。

总之，这一研究提出线粒体具有统一的信号功能，通过该功能，机械组织微环境协调互补的细胞功能。

附：英文原文

Title: Mitochondrial mechanotransduction through MIEF1 coordinates the nuclear response to forces

Author: Romani, Patrizia, Benedetti, Giada, Cusan, Martina, Arboit, Mattia, Cirillo, Carmine, Wu, Xi, Rouni, Georgia, Kostourou, Vassiliki, Aragona, Mariaceleste, Giampietro, Costanza, Grumati, Paolo, Martello, Graziano, Dupont, Sirio

Issue&Volume: 2024-10-21

Abstract: Tissue-scale architecture and mechanical properties instruct cell behaviour under physiological and diseased conditions, but our understanding of the underlying mechanisms remains fragmentary. Here we show that extracellular matrix stiffness, spatial confinements and applied forces, including stretching of mouse skin, regulate mitochondrial dynamics. Actomyosin tension promotes the phosphorylation of mitochondrial elongation factor 1 (MIEF1), limiting the recruitment of dynamin-related protein 1 (DRP1) at mitochondria, as well as peri-mitochondrial F-actin formation and mitochondrial fission. Strikingly, mitochondrial fission is also a general mechanotransduction mechanism. Indeed, we found that DRP1- and MIEF1/2-dependent fission is required and sufficient to regulate three transcription factors of broad relevance—YAP/TAZ, SREBP1/2 and NRF2—to control cell proliferation, lipogenesis, antioxidant metabolism, chemotherapy resistance and adipocyte differentiation in response to mechanical cues. This extends to the mouse liver, where DRP1 regulates hepatocyte proliferation and identity—hallmark YAP-dependent phenotypes. We propose that mitochondria fulfil a unifying signalling function by which the mechanical tissue microenvironment coordinates complementary cell functions.

DOI: 10.1038/s41556-024-01527-3

Source: https://www.nature.com/articles/s41556-024-01527-3