Several human pathologies including neurological, cardiac, infectious, cancerous, and metabolic diseases have been associated with altered mitochondria morphodynamics. Here, we identify a small organic molecule, which we named Mito‐C. Mito‐C is targeted to mitochondria and rapidly provokes mitochondrial network fragmentation. Biochemical analyses reveal that Mito‐C is a member of a new class of heterocyclic compounds that target the NEET protein family, previously reported to regulate mitochondrial iron and ROS homeostasis. One of the NEET proteins, NAF‐1, is identified as an important regulator of mitochondria morphodynamics that facilitates recruitment of DRP1 to the ER–mitochondria interface. Consistent with the observation that certain viruses modulate mitochondrial morphogenesis as a necessary part of their replication cycle, Mito‐C counteracts dengue virus‐induced mitochondrial network hyperfusion and represses viral replication. The newly identified chemical class including Mito‐C is of therapeutic relevance for pathologies where altered mitochondria dynamics is part of disease etiology and NEET proteins are highlighted as important therapeutic targets in anti‐viral research.

中文翻译：

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NEET蛋白的化学靶向揭示了它们在线粒体形态动力学中的功能

包括神经、心脏、传染性、癌性和代谢性疾病在内的几种人类疾病与线粒体形态动力学的改变有关。在这里，我们确定了一个小的有机分子，我们将其命名为 Mito-C。Mito-C 靶向线粒体并迅速引发线粒体网络断裂。生化分析表明，Mito-C 是一类新的杂环化合物的成员，其靶向 NEET 蛋白家族，此前有报道称其可调节线粒体铁和 ROS 稳态。其中一种 NEET 蛋白 NAF-1 被确定为线粒体形态动力学的重要调节剂，可促进 DRP1 募集到 ER-线粒体界面。与某些病毒调节线粒体形态发生作为其复制周期的必要部分的观察结果一致，Mito-C 抵消登革热病毒诱导的线粒体网络过度融合并抑制病毒复制。包括 Mito-C 在内的新发现的化学类别与病理学具有治疗相关性，其中线粒体动力学改变是疾病病因学的一部分，NEET 蛋白被强调为抗病毒研究中的重要治疗靶点。