近日，瑞士洛桑联邦理工学院Maurizio Molinari及其课题组开发出细胞器吞噬受体的内在紊乱区域是可互换的，并控制细胞器碎片、ER吞噬和有丝自噬通量。该项研究成果发表在2025年8月4日出版的《自然—细胞生物学》上。

在这里，该研究组发现细胞器吞噬受体由控制细胞器和亚细胞器分布的膜系固模块和具有净累积负电荷的细胞质内在无序区（IDR）组成，该区域控制细胞器碎片并显示LC3相互作用区（LIR）。LIR对于溶酶体的递送是必需的，但对于细胞器的分裂是必不可少的。内质网（ER）吞噬受体的IDRs在线粒体外膜移植时触发DRP1辅助的线粒体断裂和线粒体自噬。当线粒体自噬受体的IDRs移植到内质网膜时，会触发内质网碎片和内质网吞噬。这提供了一个关于序列散度的函数守恒的有趣例子。

他们的结果表明，通过表面表达由细胞器靶向模块和IDR模块组成的细胞器靶向嵌合体来控制胞内细胞器的完整性和活性的可能性，这些嵌合体具有净累积负电荷，如果它含有LIR，最终标记细胞器部分以进行溶酶体清除。

据介绍，细胞器吞噬受体控制其部分归巢细胞器的产生和传递到酸性降解室，以回收营养物质，去除有毒或老化的大分子，并根据生理或病理线索重塑细胞器。它们是如何运作的还不清楚。

附：英文原文

Title: The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux

Author: Rudinskiy, Mikhail, Galli, Carmela, Raimondi, Andrea, Molinari, Maurizio

Issue&Volume: 2025-08-04

Abstract: Organellophagy receptors control the generation and delivery of portions of their homing organelle to acidic degradative compartments to recycle nutrients, remove toxic or aged macromolecules and remodel the organelle upon physiologic or pathologic cues. How they operate is not understood. Here we show that organellophagy receptors are composed of a membrane-tethering module that controls organellar and suborganellar distribution and by a cytoplasmic intrinsically disordered region (IDR) with net cumulative negative charge that controls organelle fragmentation and displays an LC3-interacting region (LIR). The LIR is required for lysosomal delivery but is dispensable for organelle fragmentation. Endoplasmic reticulum (ER)-phagy receptors’ IDRs trigger DRP1-assisted mitochondrial fragmentation and mitophagy when transplanted at the outer mitochondrial membrane. Mitophagy receptors’ IDRs trigger ER fragmentation and ER-phagy when transplanted at the ER membrane. This offers an interesting example of function conservation on sequence divergency. Our results imply the possibility to control the integrity and activity of intracellular organelles by surface expression of organelle-targeted chimeras composed of an organelle-targeting module and an IDR module with net cumulative negative charge that, if it contains a LIR, eventually tags the organelle portions for lysosomal clearance.

DOI: 10.1038/s41556-025-01728-4

Source: https://www.nature.com/articles/s41556-025-01728-4