Research in Focus is a series that highlights Neurobiology faculty members’ papers in peer-reviewed journals.
A study from the lab of Alecia K. Gross, Ph.D., professor and vice chair for Research and Research Infrastructure in the Department of Neurobiology, was recently published in Aging Cell.
The paper, titled “Mitochondrial Genetic Background Shapes Baseline Retinal Function, Age-Related Bioenergetic Remodeling, and Microglial STING Phenotypes," investigated how differences in mitochondrial DNA influence retinal function, aging-related changes in mitochondrial biology, and immune responses in the retina. The study's first author was McKenna Somerville, a graduate student in the Gross Lab.
To better understand the importance of this study, we sat down with Somerville to discuss research findings.
Q: Can you describe the key findings of your recent publication?
Our study used a mitochondrial-nuclear exchange (MNX) mouse model to explore the impact that the mitochondrial genome has on retinal neuron function and immunometabolism in the context of age. Here, we found that polymorphisms in mitochondrial DNA (mtDNA) can have a big impact on baseline retinal firing. We also found that both mtDNA and age have a combined effect on mitochondrial composition, mtDNA damage burden, as well as how microglia, the resident immune cell of the central nervous system, express STING, an inflammatory protein that regulates cytokine production and release. We also found that mtDNA and age alters STING expression in microglia following acute neuronal stress. Finally, our study uncovered that as animals age, the co-localization of STING with lysosomes decreases, regardless of mtDNA background.
Q: What inspired you to pursue this area of research?
Collaboration and interdisciplinary conversations inspired us to dive into this project. Our lab specifically studies retinal biology, but as we interacted with our collaborators, specifically, Dr. Scott Ballinger, we would have conversations that centered around mitochondrial dynamics. We then became curious to how these dynamics could potentially affect the retina – one of the most energy consuming tissues in the body. Additionally, I study immunology and have a keen interest in innate immune changes with age, which finalized the angle of this project looking at how changes in mtDNA alter retinal biology and immune phenotypes.
Q: How do you plan to build on this research in your future studies?
Our current plans are centered around uncovering the molecular drivers of the changes that we show in our recent publication. Yes, we see amazing changes in the composition of the mitochondria – but what is triggering that change? Can we uncover evidence of mitochondria-nuclear genome crosstalk? We are also acutely interested to see how the differences in microglia phenotype can impact models of chronic disease.
Q: Are there potential applications or implications your findings have for treating neurological disorders?
This study provides an important perspective when thinking about how neurobiological studies translate from the bench and into the human population. mtDNA is immensely varied in sequence across the human population, and our study shows how just two DNA polymorphisms conveys significant differences in how neurons function as well as how the microglia that support neurons change phenotypically. Ultimately, the findings of our study have major implications for the treatment of neurological disorders in the face of human homogeneity.
Q: Collaboration is so important to research at UAB. Was there collaboration involved in your project and, if so, with whom?
Collaboration was integral and essential to this project. This project was completed in collaboration with Dr. Scott Ballinger, a Professor in the Division of Molecular Pathology, and mitochondrial geneticist. His team developed the MNX mouse model in collaboration with a number of other researchers. We worked very closely with him to design the experiments and interpret the findings of our study and are excited to continue working with him on future projects furthering the insights that we share in this publication.