Extract
[...] Based on various documents and using your knowledge, you will explain the reasons for this muscle weakness. Based on various documents, related to each other, and with our knowledge, we want to explain the reasons, among others, for the muscle weakness of the proximal muscles of people affected by NARP syndrome, a progressive, clinically heterogeneous disease characterized by the combination of various symptoms. Muscle weakness can thus be defined as a motor deficit or functional impotence of the muscles. Muscle contraction is a process that relies on the functionality of mitochondria, cellular organelles that are partly responsible for providing the necessary energy for survival and cellular function. [...]
[...] When there is an influx of Calcium ions then comes the 'fixation' stage of the myosin head on an actin filament. This process initiates the 'motor phase', during which we can observe a conformational change of the myosin head during the ejection of ADP and Pi, leading to a bending of the myosin head and thus a sliding of the actin filament towards the center of the sarcomere. When the contraction has thus taken place, there is then 'separation' of the myosin head which detaches from the actin filament by fixation of an ATP molecule on the myosin head, leading to a sliding of the actin filament towards the end of the sarcomere. [...]
[...] This ATP Synthase is the last key step of the enzymatic complexes of the respiratory chain seen previously. In order to evaluate whether this ATP Synthase can be involved in the muscle weakness of people affected by the NARP syndrome, we can see, on the , the evaluation of the activity of the ATP synthase, which translates to the level of oxygen consumption in cells from a healthy individual and an individual affected by the NARP syndrome, before and after the addition of ADP. [...]
[...] These results tend to determine that NARP syndrome, whose cause we previously identified by a failure of ATP synthase activity, would probably be due to a mutation of one of these enzymatic compounds rather than an absence. In order to verify this, it would be advisable to have a quantitative approach to the presence of the different enzymatic complexes of the respiratory chain and/or a genetic study of these complexes, and more precisely of the complex V ATP synthase complex. [...]
[...] There are 5 enzymatic complexes involved in the respiratory chain, which are as follows: - The complex also known as NADH-CoQ reductase - The complex II, also known as Succinate-Co Q reductase - The complex III, also known as Ubiquinol cytochrome c reductase - The complex IV, also known as cytochrome c oxidase - The complex also known as ATP Synthase These five enzyme complexes are involved in different proton movements and electron transfers between the mitochondrial matrix and the intermembrane space of the mitochondrion. Although the entire set of these complexes are essential, they allow in fine, the production of ATP molecules by the ATP Synthase complex, which we know is necessary, in particular, for muscle contraction. Muscles are composed of contractile units called sarcomeres, which are themselves made up of two types of filaments: actin thin filaments and thick myosin filaments. Their excitation thus allows for muscle contraction and relaxation. [...]
