NSF-DFG: Investigating Ribosome Tethering to Mitochondria in Dormant Yeast Cells

About This Grant

Dormancy is a survival strategy used by cells across all forms of life. When nutrients such as food and water are scarce, cells enter a low-energy state to preserve vital functions. This project will investigate how cells reorganize their machinery during dormancy, focusing on ribosomes which are molecular machines that build proteins. The research team, led by Dr. Ahmad Jomaa at the University of Virginia and Dr. Simone Mattei at the EMBL Imaging Center in Germany, recently discovered that in dormant yeast cells, ribosomes stop making proteins and hibernate by attaching themselves to fragmented mitochondria. This unexpected behavior suggests a new way that cells conserve energy during stress. The Jomaa lab will use advanced imaging and molecular biology techniques to uncover how ribosomes become inactive on mitochondria and what role this plays in helping cells survive under stress. These findings will provide fundamental insights into how life adapts to extreme conditions, with broader implications for medicine, agriculture, and biotechnology. The project also includes an educational outreach effort that researchers established called “Molecular Touch.” This program will introduce middle and high school students in small classes at the Charlottesville and Albemarle County schools to the world of structural biology using 3D-printed models of ribosomes. This initiative supports NSF’s mission by advancing discovery while expanding STEM education and workforce development. This project will investigate the molecular and cellular basis of dormancy, a reversible quiescent state that enables cells to survive under nutrient-limiting conditions. Dormancy is a conserved survival strategy observed across all domains of life, yet the mechanisms that regulate energy conservation and repression of protein synthesis during this state remain poorly understood. Recent work by the Jomaa lab at the University of Virginia and the Mattei lab at EMBL revealed a novel phenomenon in dormant Schizosaccharomyces pombe cells: Ribosomes, which normally produce proteins in the cytoplasm, become stably tethered to mitochondria and enter an inactive, hibernating state. This discovery suggests a spatially organized and regulated mechanism of translational repression during dormancy. The two teams will combine cryo-electron tomography, yeast genetics, biochemistry, and high-resolution structural biology to uncover the molecular determinants of ribosome-mitochondria tethering and its functional consequences. The specific aims are to: (1) Identify the mitochondrial receptor responsible for ribosome tethering during glucose depletion; (2) Determine how the ribosomal protein RACK1 regulates tethering, mitochondrial function, and stress survival, and; (3) Elucidate how ribosomes are released, and translation resumes upon nutrient repletion. By uncovering how cells reorganize the translational machinery during metabolic stress, this project will advance our understanding of cellular adaptation, protein synthesis regulation, and the molecular logic underlying dormancy and recovery. This project is funded by the Cellular Dynamics and Function program of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.