Issue 82 / July - August 2011
It's Not So Futile After All!
Have you ever taken apart an electronic device in order to fix it? If so, you’ll recall that sometimes, when you reassemble the device completely, one screw or piece remains in your hand and you don’t know where it should go. The device seems to work fine without the leftover part. Then you joke, “This piece was useless, I improved the design!” Nevertheless, you know that the engineers who designed the device probably didn’t include meaningless parts that have no function. Some time passes, and sooner or later, the function of that leftover piece becomes apparent when your device fails again, this time perhaps for good. The “meaningless” piece had a crucial role in the function of the device, but you couldn’t see it at first. Deeming what we don’t understand “useless” is a human response; our best and brightest are not immune. Even scientists take the same attitude when they don’t understand what something does. We see an example of this behavior in futile cycles.
Futile cycles are described as two opposing biological reactions that take place in a cell at the same time [1, 2]. As a result, futile cycles have seemingly zero net gain for the cell. Actually, because no process is 100 percent efficient, some energy is lost as heat. Thus, these cycles may even cost cells some energy. They were named “futile” cycles because scientists thought that it was wasteful for a cell to operate two exactly opposite processes simultaneously.
One such process occurs in the powerhouses of cells, the mitochondria. Mitochondria are the places where a process called “oxidative phosphorylation” takes place. Oxidative phosphorylation is an efficient way of producing ATP, the cellular energy currency . In this process, high-energy electrons in nutrients are used to generate potential energy, which is in turn used to produce ATP.
Scientists who worked on mitochondrial function were flabbergasted to discover a family of proteins in the mitochondria that had a strange function. These proteins were dissipating the potential energy in the mitochondria before it could be used to produce ATP. They were named “uncoupling proteins” because they were uncoupling the potential energy buildup from ATP production . Scientists couldn’t imagine what these wasteful proteins were doing in our mitochondria. Uncoupling proteins were decreasing the ATP production efficiency of mitochondria. Therefore, they named this process a futile cycle, where electrons from food were used for building up a potential, and an opposing action of uncoupling proteins were dissipating this potential before it could be stored as ATP . This was similar to short-circuiting a battery by connecting two poles with a wire, and just discharging the energyâ€”energy is lost but no work is done. The scientists took this process as a remnant of a random evolutionary process that was left unfinishedâ€”“futile,” with no function at all.
It took several years and the work of a different team of biologists to figure out the benefit of these uncoupling proteins . The scientists were working on the differences between wasps and honey bees. One striking difference between these species was in their ability to adapt to colder temperatures: honey bees couldn’t fly and collect pollen when the outside temperature dropped below 10 C (50 F). They had to stay in their beehives to keep warm. On the other hand, wasps could fly around in colder temperatures. The researchers discovered that the main difference that accounted for this phenomenon was that honey bees didn’t have uncoupling proteins in their mitochondria, while wasps did. Therefore, it became apparent that the main function of uncoupling proteins was to generate heat for the body to stay warm during the times when outside temperatures fell. The uncoupling proteins, it seemed, were generating heat while dissipating the potential energy (just like the wire that heats up when you connect two poles of a battery in short circuit). Later on, it was discovered that these proteins had crucial functions in all warm-blooded animals, especially in ones that hibernate during winter.
In this case, an event that initially appeared to be meaningless or even stupid turned out to be indispensible for supporting life under certain circumstances. The fact that we cannot see wisdom behind certain events does not mean they are random or meaningless. Perhaps it is just a matter of time when, in some context, the seemingly futile thing will have a vital role. So the question remains: is there really any such thing as “random” or “futile”?
1. Alberts, B., J.H. Wilson, and T. Hunt. 2008. "Molecular Biology of the Cell." 5th ed. New York: Garland Science. xxxiii, 1601, 
2. Available from: http://en.wikipedia.org/wiki/Futile_cycle#cite_note-0.
3. Nedergaard, J., D. Ricquier, and L.P. Kozak. 2005. "Uncoupling Proteins: Current Status and Therapeutic Prospects." EMBO Rep. 6(10), p. 917–21.
4. Jezek, P. and J. Borecky. 1998. "Mitochondrial Uncoupling protein may participate in futile cycling of pyruvate and other monocarboxylates." Am J Physiol, 1998. 275(2 Pt 1): p. C496–504.
5. Staples, J.F., E.L. Koen, and T.M. Laverty. 2004. "Futile Cycle Enzymes in the Flight Muscles of North American Bumblebees." J Exp Biol. 207(Pt 5): p. 749–54.