美国凯斯西储大学Xinghong Dai团队在研究中取得进展。他们的最新研究揭示了NINJ1如何介导质膜破裂，以及为什么NINJ2不能。该研究于2024年12月11日发表于国际一流学术期刊《细胞》杂志上。

研究人员表示，Ninjurin-1（NINJ1）是质膜破裂（PMR）的活跃执行因子，这一过程以前被认为是溶解性细胞死亡中的被动事件。Ninjurin-2（NINJ2）是NINJ1的近亲同源物，但无法介导PMR。

利用低温电子显微镜（cryo-EM），研究人员发现NINJ1和NINJ2都组装成一边疏水而另一边亲水的线状纤维。这一结构特征和其他证据表明，通过质膜破裂（PMR）机制，NINJ1纤维缠绕并溶解膜碎片，并且在质膜上形成孔，这种情况较少。

与直的NINJ1纤维相反，NINJ2纤维向细胞内空间弯曲，阻止其圆化甚至组装在相对平坦的膜上来介导PMR。突变研究进一步表明，NINJ2 纤维的曲率是由于与脂质（特别是胆固醇分子），在脂质双层的细胞质单层上的强结合而诱导的。

附：英文原文

Title: How NINJ1 mediates plasma membrane rupture and why NINJ2 cannot

Author: Bibekananda Sahoo, Zongjun Mou, Wei Liu, George Dubyak, Xinghong Dai

Issue&Volume: 2024-12-11

Abstract: Ninjurin-1 (NINJ1) is an active executioner of plasma membrane rupture (PMR), a process previously thought to be a passive osmotic lysis event in lytic cell death. Ninjurin-2 (NINJ2) is a close paralog of NINJ1 but cannot mediate PMR. Using cryogenic electron microscopy (cryo-EM), we show that NINJ1 and NINJ2 both assemble into linear filaments that are hydrophobic on one side but hydrophilic on the other. This structural feature and other evidence point to a PMR mechanism by which NINJ1 filaments wrap around and solubilize membrane fragments and, less frequently, form pores in the plasma membrane. In contrast to the straight NINJ1 filament, the NINJ2 filament is curved toward the intracellular space, preventing its circularization or even assembly on a relatively flat membrane to mediate PMR. Mutagenesis studies further demonstrate that the NINJ2 filament curvature is induced by strong association with lipids, particularly a cholesterol molecule, at the cytoplasmic leaflet of the lipid bilayer.

DOI: 10.1016/j.cell.2024.11.021

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01337-0