326-mTOR Regulation of Cytoskeleton Drives Mitoxyperilysis скачать в хорошем качестве

326-mTOR Regulation of Cytoskeleton Drives Mitoxyperilysis

This article by Wang et al. introduces a novel lytic cell death pathway, termed mitoxyperilysis. This process is triggered by the simultaneous occurrence of innate immune activation and metabolic disruption (IIAMD), which together cause mitochondrial oxidative stress and damage. The core mechanistic step, which the authors name mitoxyperiosis, involves damaged mitochondria maintaining prolonged physical contact with the cell's plasma membrane, resulting in lethal local oxidative damage. This sustained contact and subsequent cell death are specifically regulated by the signaling complex mTORC2, which promotes cell lysis by suppressing critical cytoskeletal activity necessary for mitochondrial retraction. Researchers demonstrated that activating the IIAMD synergy can regress tumors in mice, identifying a unique cell death modality that is independent of conventional pathways like pyroptosis or necroptosis. This research suggests a potential strategy for developing mTORC2-dependent cancer therapeutics by manipulating subcellular mitochondrial position. References: • Wang Y, Lu J, Carisey A F, et al. Innate immune and metabolic signals induce mitochondria-dependent membrane lysis via mitoxyperiosis[J]. Cell, 2025.