Centre de Recherche en Biologie cellulaire de Montpellier (CRBM), Université de Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.
Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen del Rocío-CSIC-Universidad de Sevilla, Sevilla, Spain.
Life Sci Alliance. 2022 May 13;5(9). doi: 10.26508/lsa.202101160. Print 2022 Sep.
Membrane contact sites are functional nodes at which organelles reorganize metabolic pathways and adapt to changing cues. In , the nuclear envelope subdomain surrounding the nucleolus, very plastic and prone to expansion, can establish contacts with the vacuole and be remodeled in response to various metabolic stresses. While using genotoxins with unrelated purposes, we serendipitously discovered a fully new remodeling event at this nuclear subdomain: the nuclear envelope partitions into its regular contact with the vacuole and a dramatic internalization within the nucleus. This leads to the nuclear engulfment of a globular, cytoplasmic portion. In spite of how we discovered it, the phenomenon is likely DNA damage-independent. We define lipids supporting negative curvature, such as phosphatidic acid and sterols, as bona fide drivers of this event. Mechanistically, we suggest that the engulfment of the cytoplasm triggers a suction phenomenon that enhances the docking of proton pump-containing vesicles with the vacuolar membrane, which we show matches a boost in autophagy. Thus, our findings unveil an unprecedented remodeling of the nucleolus-surrounding membranes with impact on metabolic adaptation.
膜接触位点是细胞器重新组织代谢途径并适应变化信号的功能节点。在核仁周围的核膜亚区,非常有弹性且易于扩展,可以与液泡建立接触,并响应各种代谢应激进行重塑。在使用具有不同目的的遗传毒素时,我们偶然发现了这个核亚区的一个全新重塑事件:核膜与液泡的常规接触被分割,并且在核内发生剧烈的内化。这导致了球形细胞质部分的核内包裹。尽管我们是如何发现它的,但这种现象可能与 DNA 损伤无关。我们将支持负曲率的脂质,如磷脂酸和固醇,定义为该事件的真正驱动因素。从机制上讲,我们认为细胞质的吞噬作用触发了一种抽吸现象,增强了含有质子泵的囊泡与液泡膜的对接,我们证明这与自噬的增强相匹配。因此,我们的发现揭示了核仁周围膜的一种前所未有的重塑,对代谢适应有影响。