Physical regulation of cellular respiration by membrane lipid composition

University Of California-Berkeley, Berkeley CA

Investigators

Abstract

The chemical energy that cells use for growth is generated using respiration, a universal set of reactions that occur partly within lipid membranes. Lipid composition is used by cells to modulate the properties of their membranes, which could act as important physical structures for reactions that occur during respiration. In this project, novel synthetic biology approaches will be used to investigate biophysical roles for lipid chemistry and membrane structure in respiratory activity. This research will provide mechanistic insight into respiratory function and cell physiology that is applicable to a wide variety of organisms and is relevant to understanding the interplay of diet and disease in human health. In addition to the research activities, this grant will support education and outreach efforts that focus on scientific training for underprivileged high school and undergraduate students. These efforts will teach students fundamental concepts in metabolism and provide hands-on experience with emerging biotechnology research projects in order to support their future careers in science and technology. Efforts to engineer fatty acid composition in bacteria have led to the observation that fluidizing lipid components, such as unsaturated lipids, act as a general regulator of respiratory metabolism. The project will test the hypothesis that respiratory flux by is controlled by the lipid-mediated diffusion rates of electron transport chain components. This will be done with a combination of biophysical measurements, physiological experiments, and physical modeling of bacterial respiratory chains. Lipid composition varies tremendously among prokaryotes and this could partly be understood through differences in their metabolic requirements. The project will therefore use synthetic biology approaches to assess the metabolic effects of isoprenoid-based membrane components that modulate membrane structure in a heterologous bacterial host. Lipid composition is also tightly regulated in mitochondrial membranes, which carry out respiration in all eukaryotic cells. The project will use engineered yeast strains to systematically investigate the role of fatty acid composition in mitochondrial structure and respiratory activity. These systems will serve as models for understanding how lipid composition can affect metabolic functions and may be broadly applicable to many important processes.