Collaborative Research: Defining functions of an essential, conserved protein that uniquely links the mitochondrial matrix with the cytoplasm

Complex organisms, including humans, other animals, and plants, depend on chemical energy produced in their cells by tiny cellular substructures called mitochondria that consume oxygen and release CO2. This project investigates a specific component of mitochondria essential to their function. Plants depend on photosynthesis in chloroplasts and respiration in mitochondria to convert electron transport energy to chemical energy.

While the importance of photosynthesis is well recognized, the contribution of plant mitochondrial respiration is underappreciated, even though 25 to > 50% of CO2 converted to sugars by photosynthesis is released as CO2. Defining mechanisms controlling mitochondrial function are therefore critical to plant growth and productivity. This project will uncover the mechanistic details of mitochondrial function.

The Broader Impacts of the work include the intrinsic merit of the research as mitochondria ultimately contribute to plant productivity and CO2 release which are issues critical to agriculture and climate change. Additional activities include enhancing diversity in the STEM workforce through developing a "Biotech at San Diego State University" Scholars Program (BT@SDSU) that will involve all PIs that are part of this collaborative project.

The program includes intensive lab research experiences and summer internships in biotech companies along with an ongoing scholars community focused on learning strategies and skills for career preparedness. Through continuous program improvement, BT@SDSU will serve as a model for other programs to support students who want to enter biotech careers.

This project will investigate how specific mitochondrial components integrate mitochondrial function with the rest of the plant cell, which has required the evolution of communication pathways across the mitochondrial membrane. This important question will be addressed through studies of the ATAD3 proteins (ATPase family AAA domain-containing protein 3) in plants.

These mitochondrial proteins span from the matrix to the cytosol, across both the inner and outer mitochondrial membranes, uniquely positioning them to integrate mitochondrial function within the cell. They combine a distinct C-terminal AAA+ domain located in the mitochondrial matrix and an N-terminal ATAD3-N domain of unknown function that is exposed to the cytosol.

Although linked to many mitochondrial processes, their biochemical and cellular functions remain unknown. This research seeks to understand how the AAA+ and ATAD3-N domains contribute to the essential roles of ATAD3. The project will not only uncover functions of these conserved proteins that are essential to life, but also provide new insights into how ATAD3s have evolved in the plant lineage to integrate mitochondria into the cell while training the next generation of biotech researchers.

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.