Back to article: Endocytosis in the adaptation to cellular stress

FIGURE 6: Regulation of endocytosis by oxygen stress. Under adequate oxygen supply there is limited endocytosis of the Na+/K+-ATPase, which is needed at the plasma membrane to build up the ion gradient that supports alveolar fluid clearance. When oxygen levels drop, the endocytosis of Na+/K+-ATPase is promoted to preserve energy. Hypoxia-induced ROS via an increase in Ca2+ lead to the activation of CAMKK-β which activates AMPK and PKC-ζ. PKC-γ phosphorylates sites on AP-2 and the Na+/K+-ATPase to boost Na+/K+-ATPase endocytosis. During prolonged hypoxia, the HIF pathway triggers the ubiquitination and degradation of PKC-ζ by elevating the expression of the E3 ubiquitin ligase HOIL-1L. In this way cells balance energy preservation and alveolar fluid clearance for cellular and organismal survival (see section ”Hypoxia – O2 stress” for further details).

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