Brownian dynamics simulation of cytochrome c diffusion and binding with cytochrome c1 in mitochondrial crista

• Main Authors: Abaturova Anna M., Brazhe Nadezda A., Kovalenko Ilya B., Riznichenko Galina Yu, Rubin Andrei B.
• Format: Article
• Language: English
• Published: EDP Sciences 2020-01-01
• Series: ITM Web of Conferences
• Online Access: https://www.itm-conferences.org/articles/itmconf/pdf/2020/01/itmconf_mmb2019_04001.pdf

Cytochrome c (Cc) protein shuttles electrons from respiratory chain complex III — from cytochrome c1 (Cc1) subunit — to complex IV during oxidative phosphorylation, in intermembrane space of mitochondria and cristae lumen. With Leigh syndrome (LS), the crista lumen width (CLW) increases, and ATP production declines. One of the questions raised by this situation is to find out how ATP production impairs at LS. Using the simulation of Brownian dynamics, we tested whether the increase in CLW declines respiration at the stage of electron transport of Cc to Cc1. We designed a Brownian dynamics model of horse Cc diffusion and binding with bovine Cc1 in solution by the ProKSim software. The values of the model parameters were estimated to obtain the same dependence of the second-order association rate constant on the ionic strength as in the experiment [1]. Estimated values of the model parameters were used in the model of the reaction in the cristae lumen. The model scene was a parallelepiped. The distance between the two surfaces simulated crystal membranes varied. We received increasing of half-life time of Cc diffusion and binding with Cc1 at increasing CLW. For membrane surface 90Åx100Å (close to the membrane size of complex III), the half-life time of the process changed from 0.098 to 0.22 µs with increasing cristae lumen width from 120 to 160 Å. But due to the half-life time of electron transfer between proteins in the complex, estimated in [1], is higher (100.5µs), the overall time shouldn’t change. To simulate impair of ATP production in the model with an increase in the crista lumen width, we probably need to add to the model IV complex and take into account the dimerization defect of ATP synthase.