Fig. 3: The necroptosis pathway and mitochondria. | Cell Death Discovery

Fig. 3: The necroptosis pathway and mitochondria.

From: Mitochondrial orchestration of PANoptosis: mechanisms, disease pathogenesis, and emerging therapeutic frontiers

Fig. 3: The necroptosis pathway and mitochondria.The alternative text for this image may have been generated using AI.

When caspase activity is inhibited, TNF receptor complexes form necrosomes through the RIPK1-RIPK3 kinase cascade, which drives MLKL phosphorylation and oligomerization, eventually leading to plasma membrane permeabilization and cell lysis. RIPK3 phosphorylates mitochondrial pyruvate dehydrogenase to produce superoxide anion and hydrogen peroxide (Hâ‚‚Oâ‚‚). Mitochondria-derived ROS modify RIPK1 at Cys257/Cys268 to enhance its kinase activity and promote necrosome assembly in a positive feedback manner.

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