意大利帕多瓦大学Luca Scorrano研究小组取得一项新突破。他们揭示了肿瘤血管生成和发育需要线粒体蛋白-视神经萎缩1（OPA1）。该研究于2020年4月20日在线发表在国际学术期刊《细胞-代谢》杂志上。

研究人员发现血管生成需要线粒体内膜线粒体融合蛋白OPA1。OPA1响应血管生成刺激表达水平迅速升高，以抑制激活B细胞（NFκB）信号的核因子κ轻链增强子，最终导致血管生成基因的表达和血管生成。

实际上，对于依赖NFκB途径的肿瘤血管生成和发育来说，内皮细胞Opa1是必不可少的；并且其影响肿瘤的生长和转移。一线小分子特异性OPA1抑制剂证实内皮细胞（EC） Opa1可以在药理上作为靶点减少肿瘤的生长。这些数据证实Opa1是生理上以及肿瘤血管生成的重要组成部分。

据悉，尽管EC功能受线粒体代谢的影响，但线粒体动力学在血管生成中的作用，即从现有脉管系统形成新血管的作用尚不清楚。

附：英文原文

Title: Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

Author: Stéphanie Herkenne, Olivier Ek, Margherita Zamberlan, Anna Pellattiero, Maya Chergova, Iigo Chivite, Elika Novotná, Giovanni Rigoni, Tiago Branco Fonseca, Dijana Samardzic, Andrielly Agnellini, Camilla Bean, Giulietta Di Benedetto, Natascia Tiso, Francesco Argenton, Antonella Viola, Maria Eugenia Soriano, Marta Giacomello, Elena Ziviani, Gabriele Sales, Marc Claret, Mariona Graupera, Luca Scorrano

Issue&Volume: 2020-04-20

Abstract: While endothelial cell (EC) function is influenced by mitochondrial metabolism, therole of mitochondrial dynamics in angiogenesis, the formation of new blood vesselsfrom existing vasculature, is unknown. Here we show that the inner mitochondrial membranemitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis.In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factorkappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowingangiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed requiredin an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impactingtumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitorconfirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Ourdata identify Opa1 as a crucial component of physiological and tumor angiogenesis.

DOI: 10.1016/j.cmet.2020.04.007

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30189-3