Where there’s life, there is energy. In our tissues energy is generated by specialized organelles called mitochondria  (C) often referred as power stations of the cell. 90-95% of the oxygen from the air we breathe is consumed by mitochondria to produce energy during the process called cellular respiration. Cells energy currency is called ATP (adenosine triphosphate). When ATP is broken into ADP and Pi energy is released and can be used for many needs of the body such as heart beating, brain activity, kidney functioning as well as the synthesis of proteins and DNA inside all our cells. Mitochondria constantly consume oxygen and using energy coming from foodstuff to generate ATP for cellular needs (A, B).

First, we degrade everything we ate into smaller molecules and these molecules are oxidized to produce NADH (nicotinamide adenine dinucleotide). This molecule is a carrier of  “high-energy” electrons in the cell. Mitochondrial Complex I is the only enzyme that can take these electrons from NADH and derive energy stored in there. This is one of the most important and least understood key components of the mitochondria and it initiates the processes of energy production during respiration of the cell. The structure of the mammalian enzyme was not known until recently. In August 2016 two groups, one of Judi Hirst from Cambridge, UK and another of Leonid Sazanov from Vienna, Austria published almost completely resolved structures for bovine (cow) and ovine (sheep) enzyme. Structure of human complex I is very similar, and now  we can use this knowledge to study and cure diseases of  mankind.

The mitochondrial enzyme is a huge molecule composed of at least 45 (!!) different proteins. Its’ L-shaped molecule sits in the membrane so that one arm is exposed outside and another arm is embedded into the membrane. Each time, in the exposed arm two electrons (e^-) from NADH are transfers them via a special electrical wire inside the enzyme towards the membrane. In the membrane there is an electron carrier called ubiquinone (Q-10) – it can come from the membrane to the inside of complex I molecule and take these two electrons. Now, these electrons have “lower energy”. The difference in energy does not disappear. Somehow (we do not know the exact mechanism yet), inside complex I energy of electrons is used to move membrane parts so that four protons (H⁺) are taken from one side of the membrane and actively moved on the other side (E).

With other members of the respiratory chain (complexes III and IV) complex I actively builds up a large difference in proton concentration across the membrane (D). The passive movement of these protons back via so-called ATP-synthase of complex V (which sits in the same membrane) drives the synthesis of ATP for cellular needs. Like a watermill, ATP-synthase uses the flow of protons to make ATP while Complex I pumps them back using the energy from the foodstuff. This is the way how mitochondria convert energy from the food to the cellular energy currency - namely ATP. If you are interested in general aspects of this process please read David Nicholls book “Bioenergetics-4” (or any of the earlier editions). If you would like to get into the details of complex I, please go here.