Investigating the Role of the MICOS Complex in Mitochondrial Integrity and Aging in Drosophila melanogaster
Keith Benedict, Kaden Kent, Victor Knowles
Department of Biology
Faculty Supervisor: Blake Riggs
Aging is a complex process involving cellular changes, including mitochondrial dysfunction, that contribute to tissue decline. The Mitochondrial Contact Site and Cristae Organizing System (MICOS) maintains cristae architecture, the inner membrane folds required for ATP production. Disruption of MICOS impairs mitochondrial integrity, leading to fragmentation, reduced ATP output, and increased cellular stress. However, its role in maintaining mitochondrial stability across the lifespan remains unclear. We hypothesize that MICOS loss accelerates tissue-specific aging by disrupting cristae structure and increasing oxidative stress. To test this, we investigate the disruption of the MICOS component mitofilin in Drosophila melanogaster. Gene knockout is performed using CRISPR/Cas9 and validated by RT-qPCR, with OPA1 as a positive control due to its role in mitochondrial fusion. Aging phenotypes are assessed using negative geotaxis to measure locomotor decline and lifespan assays to evaluate longevity across Cas9 wild-type, OPA1, and mitofilin knockouts. Climbing data shows that Cas9 WT outperforms both knockouts between Days 50–75, and we expect reduced lifespan in mitofilin and OPA1 knockouts. Future studies will assess oxidative damage using 8-OHdG immunostaining in brain and muscle tissue. These findings will provide insight into mechanisms driving age-related decline and diseases associated with mitochondrial dysfunction.