Description of Research Expertise

Description of Research Expertise

The Ogiso's lab has been studying studying structure and function of bacterial/mitochondrial complex I, which is the entry enzyme of the respiratory chain. Complex I plays a central role in cellular aerobic energy metabolism. Therefore, complex I dysfunctions lead to a remarkably wide range of human diseases including heart failure, type 2 diabetes, and neuronal degenerative diseases such as Parkinson's Disease. Currently, we are tackling one of the most challenging fundamental questions in bioenergetics: How is electron transfer is linked to vectorial H+ translocation in complex I?

We are also interested in how to rescue complex I dysfunction. The most crucial and unique function of complex I is NADH oxidation. Impaired NADH oxidation in mitochondria leads to lactic acidosis, high NADH/NAD+ ratio, increased reactive oxygen species (ROS), and eventually, apoptosis. One effective strategy is a complementation of dysfunctional complex I by fixing altered NADH/NAD+ balance to protect cells from excessive ROS generation. We are investigating the NAD+ metabolism in cells and animals, and searching for strategies to modulate NADH/NAD+ levels metabolically.