The Effect of Mutation of L345P in the Desmin Gene on the Process of Autophagy in Muscle Cells of the C2C12 Line

摘要

The process of autophagy plays an important role in the life of the cell, in particular, in the process of maintaining proteostasis. In muscle cells, the process of autophagy is highly dynamic due to the need for constant renewal of the degrading proteins of the Z-disk region during muscle contraction. In this case, the cytoskeleton and, in particular, intermediate filaments play a major role in maintaining the structural and functional integrity of the muscle cell. We hypothesize that disruption of the structure of intermediate filaments of muscle cells, in particular, desmin, leads to a change in the dynamics of the process of autophagy. We have demonstrated that, in C2C12 cells, a mutation of the desmin gene ( DES L345P ) leads to a significant increase in the baseline level of autophagy and the rate of degradation of cellular components due to the process of autophagy. It has been shown that, in cells with the mutation DES L345P , after stimulation of the process of autophagy by serum starvation for 2 and 4 h, the amount of LC3-II protein is halved relative to cells with wild-type desmin. The rate of conversion of LC3-I to LC3-II remains unchanged. This observation may be associated with an increase in the base level of the process of autophagy and the rate of degradation of autophagosomes for the removal of mutant aggregate forms of the desmin protein from the cell due to mutation L345P .