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Mendoza-Hoffmann, Francisco; Perez-Oseguera, Angeles; Angel Cevallos, Miguel; Zarco-Zavala, Mariel; Ortega, Raquel; Pena-Segura, Claudia; Espinoza-Simon, Emilio; Uribe-Carvajal, Salvador; Garcia-Trejo, Jose J (2018)

THE BIOLOGICAL ROLE OF THE ZETA SUBUNIT AS UNIDIRECTIONAL INHIBITOR OF THE F1FO-ATPASE OF PARACOCCUS DENITRIFICANS

Cell Rep 22(4):1067-1078
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The biological roles of the three natural F1FO-ATPase inhibitors, ε, ζ, and IF1, on cell physiology remain controversial. The ζ subunit is a useful model for deletion studies since it mimics mitochondrial IF1, but in the F1FO-ATPase of Paracoccus denitrificans (PdF1FO), it is a monogenic and supernumerary subunit. Here, we constructed a P. denitrificans 1222 derivative (PdΔζ) with a deleted ζ gene to determine its role in cell growth and bioenergetics. The results show that the lack of ζ in vivo strongly restricts respiratory P. denitrificans growth, and this is restored by complementation in trans with an exogenous ζ gene. Removal of ζ increased the coupled PdF1FO-ATPase activity without affecting the PdF1FO-ATP synthase turnover, and the latter was not affected at all by ζ reconstitution in vitro. Therefore, ζ works as a unidirectional pawl-ratchet inhibitor of the PdF1FO-ATPase nanomotor favoring the ATP synthase turnover to improve respiratory cell growth and bioenergetics.