RUI: Exploring the Function of FtsZs and the Cytoskeleton to Determine the Molecular Mechanism of Mitochondrial Dynamics in Dictyostelium discoideum

University Of Central Arkansas, Conway AR

Investigators

Abstract

Cellular mitochondria regulate many processes, such as calcium levels and programmed cell death. However, they are best known for energy transduction and are often referred to as the powerhouse of the cell. This project focuses on mitochondrial structure because without appropriate structure, mitochondria become dysfunctional. Although mitochondria developed from an ancestral bacterial cell, different organisms (e.g., humans, amoeba, algae, yeast, etc.) maintain mitochondrial structure in different ways. If we can understand the mechanisms that maintain structure across these organisms, we can learn why the mechanisms are different while also gaining insight into the causes of mitochondrial dysfunction. The broader impacts of this project include the intrinsic merit of the work as the vast majority of eukaryotic cells contain these organelles. Other activities will involve K-16 students. Students at a primarily undergraduate university in central Arkansas will carry out this project. Exposure to quality, well-funded research provides students the ability to explore whether research is an appropriate career choice for them. It prepares students for doctoral programs, and mentoring students in research is critical for retention of those from groups traditionally underrepresented in STEM. In addition to training undergraduates, this project involves outreach to K-6 students. The plan is to formalize relationships with local elementary schools, specifically ones whose ACT Aspire scores indicate a deficit in science. Interactions with K-6 students via hands-on-activities are designed to inspire students, show them that science is fun, and continue to develop their scientific inquiry skills. The essential functions of the mitochondria are dependent upon their structure, which, in turn, is dependent upon mitochondrial dynamics, fission, fusion, and motility. In many cell types such as mammalian and yeast cells, a protein family known as dynamin-related proteins (DRPs) maintains the highly interconnected network of mitochondria. Importantly, our model organism, Dictyostelium discoideum does not use DRPs to regulate mitochondrial dynamics. Rather, the D. discoideum genome encodes two proteins, FszA and FszB, which are derived from the bacterial cell division protein, FtsZ. It is not understood why some organisms use DRPs and some use what appears to be derived FtsZ proteins. A long-term goal of this research is to understand the molecular mechanism of mitochondrial dynamics in D. discoideum in order to identify when and why some organisms replaced FtsZs with DRPs as they evolved. The first project goal is to identify the role of extant FtsZs in mitochondrial dynamics and will involve altering protein levels, identifying interacting proteins, and analyzing FtsZs structural complexes. Recent work has shown that the cytoskeleton is a major player in the regulation of mitochondrial dynamics, and the second goal of this project is to study the relationship of the cytoskeleton with mitochondrial dynamics by identifying fission/fusion events, along with transport velocities when the cytoskeleton is disrupted. Completion of this project will help determine if FtsZs function like DRPs, and how the D. discoideum cytoskeleton regulates mitochondrial dynamics. Ultimately, this work will contribute to understanding the evolution of mitochondria and mitochondrial dynamics and specifically why some organisms use DRPs and some use FtsZs. This project is jointly funded by the Division of Molecular and Cellular Biosciences and the Established Program to Stimulate Competititive Research (EPSCoR). 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.