I heard about the rotation of ATP synthase in a biochemistry course. The professor said it will rotate counterclockwise. Is that true? If so, what mechanism defines its direction?


1 Answer 1


Short answer
The direction of rotation depends on the viewing point of the observer and the reaction catalyzed by the ATP synthase. When synthesizing ATP, and viewed 'from the bottom' (observer faces the intermembrane space looking into the mitochondrial matrix) it rotates clockwise.

ATP synthase is a membrane bound enzyme with two large subunits; F0 and F1. F0 is inserted in the membrane and funnels H+ ions from the intermembrane space into the mitochondrial interior (Fig. 1). The stalk region connection F0 and F1 contains the γ subunit, which basically forms a rotating shaft powered by the flow of H+. This causes the entire F1 unit to rotate during ATP synthesis.

Now importantly to know before continuing; enzymes basically work two ways, as they merely establish equilibrium. As such, any ATP synthase is also an ATP hydrolase. When it synthesizes ATP, the γ subunit runs in clockwise direction when observed from the “bottom” (the side closest to the F0 and the membrane, see Fig. 2). When it hydrolyzes ATP (e.g., under non-physiological laboratory conditions) it runs counter-clockwise as the reaction, as well as the movement of the γ subunit reverses (Nakamoto, 2008).

The direction in which the rotation takes place is dependent on the steps involved (Fig. 3). In this figure, ATP hydrolysis is shown and that can be compared to burning fuel in a combustion engine. Now the direction of H+ reverses, against its concentration gradient and needing energy (the road speeding below a car if you like). Because ATP binding, hydrolysis and release of waste (ADP + Pi) each cause a 120o turn of the rotor, the F1 subunit rotates one full turn in each cycle (Yoshida, 2001). During ATP synthesis the opposite direction is established, as waste (ADP + Pi) is taken in and phosphorylated to ATP, during which the flow of H+ reverses (akin to a car going downhill, only combustion engines cannot generate gas from carbon dioxide and water, unfortunately).

![![ATP synthase
Fig. 1. ATP synthase subunits. source: Penn State University

ATP synthase
Fig. 2. ATP synthase. source: Noji, 2004

ATP synthase steps
Fig. 3. ATP synthase compared to a combustion engine. A combustion engine converts fuel energy into rotation of a rotor. It can drive the intake of the fuel gas, compression, ignition and exhaust sequentially just by a simple rotation of the central rotor (right panel). The F1 gamma-subunit has and three reaction chambers (the catalytic beta-subunits (left panels). The three reaction sites each go through three cyclic steps in a 120° phase difference to cause rotary motion, very similar to a combustion engine. source: Yoshida, 2001

- Nakamoto, Arch Biochem Biophys (2008); 476(1): 43–50
- Noji, Biohistory journal (Winter, 2004)
- Yoshida, Nature Rev Mol Cell Biol (2001); 2: 669-77

  • 1
    $\begingroup$ It should be F_o instead of F_0 $\endgroup$
    – latra
    Mar 29, 2017 at 3:15
  • 2
    $\begingroup$ Why does it rotate in that direction? $\endgroup$
    – latra
    Mar 29, 2017 at 8:12
  • $\begingroup$ @latra figure three shows why. $\endgroup$
    – AliceD
    Mar 29, 2017 at 8:13
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    $\begingroup$ I have read the caption of figure 3 and the third paragraph, but it only says ATP synthase is similar to a combustion engine. It did not tell me why that direction. $\endgroup$
    – latra
    Mar 29, 2017 at 8:42
  • $\begingroup$ @latra I can't explain it in more detail. Why does the crankshaft of an engine rotates left or right; because it is structurally engineered to do so. $\endgroup$
    – AliceD
    Mar 29, 2017 at 9:07

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