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 channel 1 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.

线粒体膜定义了不同的结构和功能区室。线粒体内膜 (IMM) 的嵴作为独立的生物能量单位发挥作用，经历快速和短暂的重塑，但这种分隔组织的意义尚不清楚¹ 。使用超分辨率显微镜，我们发现，缺乏线粒体外膜或线粒体基质的细胞质 IMM 囊泡是在静息状态下形成的。这些源自 IMM (VDIM) 的囊泡是由 IMM 突出通过线粒体外膜中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，线粒体附近的溶酶体吞噬了突出的 IMM，并在运输机械所需的内体分选复合物的帮助下，导致在类似微自噬的过程中形成 VDIM，从而保留了细胞器的其余部分。经历氧化应激的线粒体中 VDIM 的形成增强，表明它们在维持线粒体功能中的潜在作用。此外，VDIM 的形成需要活性氧激活的溶酶体钙通道、瞬时受体电位粘脂蛋白 1 释放钙，这显示了维持线粒体稳态的细胞器间通讯途径。因此，IMM 区室化可以允许通过 VDIM 选择性去除受损的 IMM 部分，这应该可以保护线粒体免受局部损伤。我们的研究结果展示了线粒体内质量控制的新途径。