线粒体直接与核孔复合物相互作用，这一成果由亚利桑那大学Hesham A. Sadek研究组经过不懈努力而取得。这一研究成果发表在2026年6月10日出版的国际学术期刊《自然》上。

在这里，该课题组研究人员确定了线粒体和核孔之间的直接相互作用。通过GST pull - down和BioID两种无偏见的蛋白质组学筛选，该研究团队发现VDAC1是与丝状核孔蛋白RANBP2相互作用的首选线粒体候选蛋白。体外CRISPR敲除RANBP2、截断RANBP2或定点诱变RANBP2-VDAC1相互作用氨基酸导致线粒体-核核接近度降低、核ATP和磷酸肌酸水平降低。在体外实验中，细胞核磷酸化蛋白组水平下降，参与组蛋白修饰、细胞分化和转录调控的通路下调。

此外，小鼠体内RANBP2 c端结构域的缺失导致胚胎死亡，原因是心脏和神经嵴分化缺陷。总的来说，这些结果描述了线粒体直接与核孔复合物相互作用的机制，这一现象对细胞核能量学和细胞分化的调节至关重要。毫无疑问，这种相互作用的其他作用仍有待揭示。

据介绍，线粒体通过与其他细胞器的直接或间接相互作用来调节细胞过程。一个被充分研究的例子是在线粒体相关的内质网膜上与内质网接触，它控制氧化还原和钙稳态等途径。最近的研究也报道了癌细胞和酵母中的线粒体-核膜直接接触可促进促生存信号传导。

附：英文原文

Title: Mitochondria directly interact with the nuclear pore complex

Author: Menendez-Montes, Ivan, Marin-Vicente, Consuelo, Mukherjee, Shibani, Ahmed, Mahmoud Salama, Gomez, Manuel Jose, Anene-Nzelu, Chukwuemeka George, Lee, Chang Jie Mick, Koslowski, Svenja, Solmonson, Ashley, Tassin, Tara, Ali, Shah R., Pessoa, Pedro, Elnwasany, Abdallah, Lam, Nicholas T., Thet, Suwannee, Calvo, Enrique, Cardoso, Alisson C., Pereira, Ana Helena M., Xiao, Feng, Wang, Ping, Mohamed, Asim, El-feky, Hamed, Elghamry, Ahmed, Gancedo-Alonso, Gonzalo, Nguyen, Ngoc Uyen Nhi, Hsu, Ching-Cheng, Westfall, Aundrea K., DeBerardinis, Ralph, Foo, Roger Sik-Yin, Kinter, Michael, Press, Steve, Xing, Chao, Szweda, Luke, Aroumougame, Asaithamby, Sanchez-Cabo, Fatima, Enriquez, Jose Antonio, Torres, Miguel, Vazquez, Jesus, Sadek, Hesham A.

Issue&Volume: 2026-06-10

Abstract: Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5. Here we identify direct interactions between mitochondria and nuclear pores. Using two unbiased proteomic screens, GST pulldown and BioID, we found that VDAC1 was the top mitochondrial candidate that interacts with the filamentous nuclear pore protein RANBP2. In vitro RANBP2 CRISPR knockout, RANBP2 truncation or site-directed mutagenesis of RANBP2–VDAC1 interacting amino acids resulted in reduced mitochondria–nucleus proximity and decreased nuclear ATP and phosphocreatine levels. This was accompanied by a decline in the levels of the nuclear phosphoproteome and downregulation of pathways involved in histone modification, cellular differentiation and transcriptional regulation in vitro. Moreover, deletion of the RANBP2 C-terminal domain in vivo in mice resulted in embryonic lethality due to cardiac and neural crest differentiation defects. Collectively, these results describe a mechanism by which mitochondria directly interact with the nuclear pore complex, a phenomenon critical for regulation of nuclear energetics and cellular differentiation. Undoubtedly, additional roles of this interaction remain to be revealed.

DOI: 10.1038/s41586-026-10588-3

Source: https://www.nature.com/articles/s41586-026-10588-3