Convergent Mitochondrial and Oxidative Stress Signatures in Spaceflight and Tauopathy: A Comparative Multi-Omics Reanalysis in Drosophila melanogaster

Abstract

Mitochondrial dysfunction is a shared biological thread between terrestrial Alzheimer's disease (AD) and in the unique stress environment of spaceflight, making mitochondrial pathophysiology a compelling target for comparative investigation. In AD, mitochondrial impairment is closely linked to defective oxidative phosphorylation, reactive oxygen species accumulation, calcium dysregulation, and neuronal injury, while spaceflight stressors such as microgravity and radiation disrupt mitochondrial homeostasis and increase oxidative stress. Understanding how the extreme stressors of spacelight affect mitochondrial function may provide insights into conserved mitochondrial stress responses and their implications for neurodegenerative diseases, including AD. Our study compares datasets from ground control Drosophila melanogaster RNA-seq with isolated radiation and microgravity exposure to discern conserved mitochondrial pathways and molecular signatures that may provide insights into AD mechanisms.