Fig. 6: Schematic illustration of mitochondrial swelling and rupture following mPTP opening, leading to the release of multiple pro-death factors: Cyt c, AIF, PNPT1, and mtDNA. | Cell Death Discovery

Fig. 6: Schematic illustration of mitochondrial swelling and rupture following mPTP opening, leading to the release of multiple pro-death factors: Cyt c, AIF, PNPT1, and mtDNA.

From: Nano-flow cytometry unveils mitochondrial permeability transition process and multi-pathway cell death induction for cancer therapy

Fig. 6

Upon mPTP opening, Cyt c is released into the cytoplasm, play a crucial role in triggering cell death pathways in a caspase-dependent manner through the formation of apoptosome. AIF translocates from the IMS to the cytoplasm and nucleus, inducing caspase-independent peripheral chromatin condensation and large-scale DNA fragmentation, contributing to cell death programs. In addition, the rupture of the outer membrane facilitates PNPT1 and mtDNA release into the cytoplasm. PNPT1, a 3’-to-5’ exoribonuclease, is released from the IMS, initiating the apoptotic decay of RNAs lacking 3’ structures and enhancing apoptosis by reducing the expression of unstable anti-apoptotic proteins. Meanwhile, the release of mtDNA induces inflammation and type I interferon responses via the cytoplasmic cGAS-STING DNA sensing pathway, thereby enhancing anti-tumor immune responses.

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