Regulation of vascular tone by a secreted mitochondrial peptide

The F0F1 ATP synthase is a large, multi-subunit complex expressed in the mitochondrial inner membrane, where it uses the energy from oxidative phosphorylation to generate ATP. Surprisingly, this complex can also be found on the plasma membrane of endothelial and other cells, and the fact that it appears to be biologically active suggests that most or all of its components can be assembled at this location. Osanai and coworkers have previously argued that the peptide coupling factor 6 (CF6), an essential component of the ATP synthase, also serves a distinct physiological role as a circulating hormone. Here, they show that CF6 localizes to and is shed from the endothelial cell surface. Endogenous peptide is highly expressed in aortae from hypertensive rats, and the authors show that a blocking antibody to the peptide can lower blood pressure in these animals, as well as in healthy controls. Recombinant peptide, conversely, induces hypertension, apparently by suppressing the synthesis of the vasodilator prostacyclin while leaving other aspects of prostanoid metabolism intact. Agents that block this endogenous vasoconstrictor might thus provide a useful means to control hypertension.

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