Proton Across the Membrane: NUST MISIS Physicists Demystify Biochemical Mechanism of Proton Transport in Mitochondria

Microbiologists and biophysicists from NUST MISIS and scientists from the Johannes Kepler University have managed to answer some major scientific questions on the global scale. Their answers help to understand how food turns into a substance that provides energy to muscles. The cycle of transformation is so complicated that its in-depth explanation can span the length of a textbook. In general, it can be presented in this way: once the food is chewed and swallowed, it enters the stomach where with the help of several mechanisms the food is partially divided into smaller parts and even molecules. The digestion process continues in the small intestine under the influence of various food enzymes. The transformation of carbohydrates into glucose, and the breaking down of lipids and protein take place there. There, the remains split into two parts and in this form (called pyruvate) enters the mitochondria, which is the binding organelle for cells in most living organisms - animals, plants, fungi.

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Glucose parts are oxidized quickly and consistently in mitochondria. The nicotinamide adenine dinucleotide (NAD) floats nearby, the proton of which is detached because of this oxidation. This proton somehow gets into the part of the mitochondria responsible for Adenosine Triphosphate - the «human gasoline», on which our whole organism runs. Until recently it wasn't clear how exactly they got there. These protons may go anywhere they want to, but they somehow stay near the membrane, flocking to the entrance of the circular gates «of the reactor for ATF synthesis». Now NUST MISIS scientists and their colleagues know why exactly this happens.

«Protons moving inside mitochondria remain inside the watery part. It is known that water molecules (H₂O) consist of two hydrogen atoms (H) and one oxygen atom (O). In addition to chemical bonds within one water molecule, these atoms can form weak bonds with neighboring water molecules, called hydrogen. Near membrane surface, these bonds in water molecules are formed in a special way because there is water on one side, and a «wall» on the other. Hydrogen bonds near membrane are different: with different quantities and structures. The proton uses them as «rails» to move forward along the membrane. Our research has demonstrated that it "likes" this structure: it doesn't float away into the mitochondria, but quickly moves along the membrane», explained Sergei Akimov, research fellow at the NUST MISIS Department of Theoretical Physics & Quantum Technologies.

The result of this fundamental research brings scientists to an understanding of global mechanisms for energy generation in cells, as well as how to open up prospects for pharmacology. The research's results can be used to develop drugs that neutralize effects of dissociative poisons, as well as for prevention of diseases connected with hyperfunction in the thyroid gland. With these diseases, the so-called substance-uncouplers (weak fat-soluble acids which effectively bind protons, resulting in an overall decrease of ATF synthesis) accumulate in mitochondria. The knowledge obtained by Russian scientists will allow the scientific community to understand what needs to be done to restore human energy in every cell.

Source: http://en.misis.ru/university/news/science/2017-10/4950/