Lysosomes drive the piecemeal removal of mitochondrial inner membrane. This study reveals that lysosomes facilitate the selective removal of damaged sections of the mitochondrial inner membrane (IMM) through a process called microautophagy-like activity. The study shows that cytosolic IMM-derived vesicles (VDIMs) are formed when the IMM herniates through pores in the outer mitochondrial membrane (OMM) created by the voltage-dependent anion channel (VDAC1). These vesicles are then engulfed by lysosomes, leading to the removal of damaged IMM sections without affecting the rest of the organelle. This process is enhanced under oxidative stress and involves calcium release via the lysosomal calcium channel TRPML1, indicating inter-organelle communication. The study also demonstrates that VDIMs are formed through ESCRT machinery-mediated membrane scission, and that this process is regulated by the interaction between TRPML1 and VDAC1. The findings suggest that IMM compartmentalization allows for the selective removal of damaged IMM sections, which could protect mitochondria from localized injury. The study provides a new pathway of intramitochondrial quality control, highlighting the role of lysosomes in maintaining mitochondrial homeostasis.Lysosomes drive the piecemeal removal of mitochondrial inner membrane. This study reveals that lysosomes facilitate the selective removal of damaged sections of the mitochondrial inner membrane (IMM) through a process called microautophagy-like activity. The study shows that cytosolic IMM-derived vesicles (VDIMs) are formed when the IMM herniates through pores in the outer mitochondrial membrane (OMM) created by the voltage-dependent anion channel (VDAC1). These vesicles are then engulfed by lysosomes, leading to the removal of damaged IMM sections without affecting the rest of the organelle. This process is enhanced under oxidative stress and involves calcium release via the lysosomal calcium channel TRPML1, indicating inter-organelle communication. The study also demonstrates that VDIMs are formed through ESCRT machinery-mediated membrane scission, and that this process is regulated by the interaction between TRPML1 and VDAC1. The findings suggest that IMM compartmentalization allows for the selective removal of damaged IMM sections, which could protect mitochondria from localized injury. The study provides a new pathway of intramitochondrial quality control, highlighting the role of lysosomes in maintaining mitochondrial homeostasis.