The spatio-temporal organization of mitochondrial F1FO ATP synthase in cristae depends on its activity mode
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MitochondriaSpatio-temporal organizationSuperresolution microscopyUltrastructureMetabolic adaptation
Salewskij, K., Rieger, B., Hager, F., Arroum, T., Duwe, P., Villalta, J., ... & Dellmann, T. (2020). The spatio-temporal organization of mitochondrial F1FO ATP synthase in cristae depends on its activity mode. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1861(1), 148091.
SponsorshipThis work was supported by the DFG (INST 190/167-2).
F1FO ATP synthase, also known as complex V, is a key enzyme of mitochondrial energy metabolism that can synthesize and hydrolyze ATP. It is not known whether the ATP synthase and ATPase function are correlated with a different spatio-temporal organisation of the enzyme. In order to analyze this, we tracked and localized single ATP synthase molecules in situ using live cell microscopy. Under normal conditions, complex V was mainly restricted to cristae indicated by orthogonal trajectories along the cristae membranes. In addition confined trajectories that are quasi immobile exist. By inhibiting glycolysis with 2-DG, the activity and mobility of complex V was altered. The distinct cristae-related orthogonal trajectories of complex V were obliterated. Moreover, a mobile subpopulation of complex V was found in the inner boundary membrane. The observed changes in the ratio of dimeric/monomeric complex V, respectively less mobile/more mobile complex V and its activity changes were reversible. In IF1-KO cells, in which ATP hydrolysis is not inhibited by IF1, complex V was more mobile, while inhibition of ATP hydrolysis by BMS-199264 reduced the mobility of complex V. Taken together, these data support the existence of different subpopulations of complex V, ATP synthase and ATP hydrolase, the latter with higher mobility and probably not prevailing at the cristae edges. Obviously, complex V reacts quickly and reversibly to metabolic conditions, not only by functional, but also by spatial and structural reorganization.