The role of mitochondrial dysfunction in immune response and mitochondrial thermogenesis

Abstract

Mitochondria are crucial for cellular energy metabolism and immune regulation, particularly through pathways involving innate immunity, and mitochondrial thermogenesis. This thesis deals with the role of mitochondrial dysfunction in immune responses and mitochondrial thermogenesis using Drosophila melanogaster as a model. RNA interference (RNAi) was used to knock down the small mitoribosomal subunit protein 28 (mRpS28) in the fat body and gut, tissues central to Drosophila’s immune defense. Following infection with Providencia rettgeri, both RNAi fly lines mRpS28-GD and mRpS28-KK showed improved survival compared to controls, with the mRpS28-KK line showing a statistically significant increase (P = 0.0009). These results support the concept of mitohormesis, as mild mitochondrial dysfunction may enhance immune resistance. In parallel, an optimized protocol was developed using the temperature-sensitive fluorescent dye MitoThermo Yellow (MTY) for measuring mitochondrial heat production from Drosophila whole body extracts. Results showed that both RNAi lines exhibited a greater temperature change (−ΔT) than the control but the changes were not statistically significant, likely insufficient number of repeats due to time limitation. Together, our findings demonstrate that mitochondrial dysfunction via mRpS28 knockdown enhances both infection resilience and alters heat production via mitochondrial inner membrane, highlighting a complex relationship between mitochondrial stress, immune response, and bioenergetic adaptation in Drosophila. The optimized MTY-based thermometry assay provides a valuable tool for studying the role of mitochondrial heat production in immune system in insect models.