Timing of complex I activity and lifespan control

The electron transport chain (ETC) is composed of several complexes, including complex I (CI), and is the base of oxidative phosphorylation in mitochondria. CI subunit genes are associated with diseases and CI impairments have been linked to longer and shorter lifespans in model organisms. Stefanatos et al. show that CI dysfunction differentially affects the lifespan of Drosophila depending on the timing of dysfunction.

The researchers generated inducible CI subunit depletion Drosophila models; CI defects during development shortened lifespan, whereas CI dysfunction in adult flies did not. Flies with impaired CI function from development showed increased sensitivity to stress, such as starvation. RNA-sequencing analyses in flies with perturbed CI activity during development revealed a signature of dysregulated energy metabolism and translation. Metabolomic and proteomic analyses suggested that changes to metabolic pathways in tissues such as the fat body are associated with reduced lifespan in flies with developmental CI disruption.