Regulation of the cardiac Na⁺ pump by palmitoylation of its catalytic and regulatory subunits

The Na⁺/K⁺-ATPase (Na⁺ pump) is the principal consumer of ATP in multicellular organisms. In the heart, the Na⁺ gradient established by the pump is essential for all aspects of cardiac function, and appropriate regulation of the cardiac Na⁺ pump is therefore crucial to match cardiac output to the physiological requirements of an organism. The cardiac pump is a multi-subunit enzyme, consisting of a catalytic α-subunit and regulatory β- and FXYD subunits. All three subunits may become palmitoylated, although the functional outcome of these palmitoylation events is incompletely characterized to date. Interestingly, both β- and FXYD subunits may be palmitoylated or glutathionylated at the same cysteine residues. These competing chemically distinct post-translational modifications may mediate functionally different effects on the cardiac pump. In the present article, we review the cellular events that control the balance between these modifications, and discuss the likely functional effects of pump subunit palmitoylation.