加拿大病童医院Nicola L. Jones和Maximiliano G. Gutierrez课题组在研究中取得进展。他们发现了溶酶体驱动线粒体内膜的碎片去除。相关论文于2024年8月21日发表在《自然》杂志上。

利用超分辨率显微镜，研究团队发现静息状态下形成的胞质自线粒体内膜嵴囊泡，没有线粒体外膜或线粒体基质。这些源自线粒体内膜嵴的囊泡(VDIM)是由线粒体外膜嵴通过电压依赖性阴离子通道1形成的孔形成的。

活细胞成像显示，靠近线粒体的溶酶体吞噬了突出的线粒体内膜嵴，并在运输机制所需的内体分选复合体的帮助下，导致源自线粒体内膜嵴的囊泡在微自噬样过程中形成，保留了细胞器的其余部分。在氧化应激的线粒体中，源自线粒体内膜嵴的囊泡的形成增强，表明它们在维持线粒体功能方面的潜在作用。

此外，源自线粒体内膜嵴的囊泡的形成需要活性氧激活的钙释放，溶酶体钙通道，瞬时受体电位粘磷脂1，显示了维持线粒体稳态的细胞器间通讯途径。因此，线粒体内膜嵴的区隔化可能允许通过源自线粒体内膜嵴的囊泡选择性去除受损的线粒体内膜嵴部分，这会保护线粒体免受局部损伤。他们的发现显示了线粒体内质量控制的新途径。

据了解，线粒体膜定义了不同的结构和功能区室。线粒体内膜嵴(IMM)作为独立的生物能量单元，经历快速和短暂的重构，但这种区隔组织的意义尚不清楚。

附：英文原文

Title: Lysosomes drive the piecemeal removal of mitochondrial inner membrane

Author: Prashar, Akriti, Bussi, Claudio, Fearns, Antony, Capurro, Mariana I., Gao, Xiaodong, Sesaki, Hiromi, Gutierrez, Maximiliano G., Jones, Nicola L.

Issue&Volume: 2024-08-21

Abstract: Mitochondrial membranes define distinct structural and functional compartments. Cristae of the inner mitochondrial membrane (IMM) function as independent bioenergetic units that undergo rapid and transient remodelling, but the significance of this compartmentalized organization is unknown1. Using super-resolution microscopy, here we show that cytosolic IMM vesicles, devoid of outer mitochondrial membrane or mitochondrial matrix, are formed during resting state. These vesicles derived from the IMM (VDIMs) are formed by IMM herniation through pores formed by voltage-dependent anion channel1 in the outer mitochondrial membrane. Live-cell imaging showed that lysosomes in proximity to mitochondria engulfed the herniating IMM and, aided by the endosomal sorting complex required for transport machinery, led to the formation of VDIMs in a microautophagy-like process, sparing the remainder of the organelle. VDIM formation was enhanced in mitochondria undergoing oxidative stress, suggesting their potential role in maintenance of mitochondrial function. Furthermore, the formation of VDIMs required calcium release by the reactive oxygen species-activated, lysosomal calcium channel, transient receptor potential mucolipin 1, showing an interorganelle communication pathway for maintenance of mitochondrial homeostasis. Thus, IMM compartmentalization could allow for the selective removal of damaged IMM sections via VDIMs, which should protect mitochondria from localized injury. Our findings show a new pathway of intramitochondrial quality control.

DOI: 10.1038/s41586-024-07835-w

Source: https://www.nature.com/articles/s41586-024-07835-w