TotM: Mammal uncoupled proton transporter, a useful useless machine

800px-Car_fire_6.24.2004-1.jpgHave you ever put a running laptop on your lap for a long time? If you were running something computationally heavy, like a complex simulation for your scientific work or a relatively fancy videogame, the computer would have heated quite quickly. Similarly, it is not advisable to check a motor engine if you have been driving before, just like it is not a good idea to touch a light bulb that has been on for one hour - at least the old ones. Even a machine that is made to keep stuff cold, like a fridge or air conditioner, has some parts  that get really hot when working for long time. The reason for this is purely thermodynamical. All those machines are converting a form of energy into another desired one: controlled electronic impulses through a silicon circuit, movement or light. But the desired energy conversion is only a fraction of the total energy input. Conducting electricity or moving a joint generate resistance or friction, which causes the energy to be lost into useless vibration of the surrounding molecules. Even worse, machines are made of delicate components that, at least some of them, may not work properly over a certain temperature, thus raising the need of refrigeration. An ideal machine should reduce to zero the energy fraction that is lost by thermal dissipation, although that theoretical limit is impossible due to the second law of thermodynamics.

Surprisingly (or not), there is a biological example that is pretty close to the theoretical ideal machine. Embedded on the membrane of many bacteria, mitochondria and chloroplasts, the ATP synthases have one of the highest known efficiencies. These tiny machines are similar to a windmill, using a flux of protons (instead of wind) to move a wheel that makes something useful: synthesize ATP from phosphate and ADP. Naturally, it requires a proton flux, that is produced by other machines. Imagine for a moment a mutated version of this protein that has lost the ATP synthase activity. Such hypothetical machine would be just a leak in the hard earned proton gradient, producing nothing in exchange but the undesired thermal noise. An organism that harbours a protein like that should be in a great disadvantage, an ideal prey for the merciless claws of natural selection.

 

10090-infrared-image-of-a-cow-pv.jpgHumans have three of such uncoupling proteins (UCP) encoded in their genomes. They are not odd, since most mammals also have three paralogs, as we can observe in our tree of the month. In the case of cows (Bos taurus), the ortholog of human UCP1 has even duplicated recently. The three genes originated at two duplication events in the base of vertebrates, and some other independent duplications can be observed in bony fishes, but why?

 

We have said that heat is an undesired and unavoidable byproduct of the conversion between two forms of energy. But what happens if we really want to heat stuff? Think of an oven or a stove. In the case of an electric one, what they do is just apply an electric current through something that is not a good electric conductor, a resistance. This, conceptually, is a very useless task, aimed to waste energy. And that’s exactly the point. The wasted energy has to dissipate somehow, and the most easy way to do that is by the most disordered form of energy, heat. Uncoupled transport proteins, also known as thermogenins, serve to the same goal: to heat the organism.

 

sleeping-baby.jpgWhile many organisms benefit of having a minimal temperature for their physiological functions, such as muscular contraction -that is why you warm up before exercising-, only a handful have the need of a constant body temperature: basically birds and mammals. Muscular contraction is a very common way to keep the body hot, a process called shivering. However, shivering has some disadvantages too. If you shiver to raise your temperature, any movement you realize is wasted energy! Even more, shivering makes noise, which could lead to a predator spotting you. Early mammals developed a new type of tissue that specializes in storing fatty acids and burning them for producing heat. The proteins needed for this function were already present in the lineage of vertebrates long before the development of endothermic capabilities and its ancient function seems to be related to protection of oxidative stress. This novel tissue is known as brown fat, and is made of a highly mitochondria rich type of adipocytes. Unlike white fat tissue, that is basically devoided of mitochondria, brown fat can burn their energy stocks in situ to produce heat. In the case of humans, brown fat is very prevalent in babies, giving them their chubby healthy cheeks. Babies are small, so they can lose heat rapidly. Even more, they do not have musculature to shiver the problem out. The synthesis of the protein is regulated by a hormonal signal that depends on the sympathetic nervous system as response to cold. Just remember that thermogenins are no excuse to not wrap yourself properly in winter, even if in theory sounds like a good way to burn fat.

 

References:

https://www.ncbi.nlm.nih.gov/pubmed/25966796

https://www.ncbi.nlm.nih.gov/pubmed/25224037

https://www.ncbi.nlm.nih.gov/pubmed/23860571

https://www.ncbi.nlm.nih.gov/pubmed/21196381

https://www.ncbi.nlm.nih.gov/pubmed/17971503

https://www.ncbi.nlm.nih.gov/pubmed/15886331

 

Pictures:

All images are under Public domain license