Fig. 10: A schematic model of C15ORF48-induced, stress-independent autophagy.

The mitochondrial protein, C15ORF48, a subunit of electron transport chain complex IV, is highly expressed in several cancer cells and thymic epithelial cells, and NF-κB signaling is important for its expression. C15ORF48 reduces mitochondrial activity and intracellular ATP levels, thereby inducing autophagy via pro-autophagic AMPK-ULK1 signaling independently of starvation or mitochondrial stress. C15ORF48-induced autophagy in cancer cells increases intracellular glutathione levels and prevents oxidative stress. C15ORF48-induced autophagy in thymic epithelial cells regulates self-tolerance and prevents autoimmunity.