Simulated Microgravity Reprograms Host Cell Architecture and Mitochondrial Function, Altering Toxoplasma gondii Growth

Simulated microgravity (SMG or μG) influences Toxoplasma gondii growth and modifies the cellular structure and function of the host cells. As an obligate intracellular parasite, Toxoplasma gondii depends on the metabolic activity and mitochondrial function of its host. However, the impact of SMG on host–pathogen interactions remains unclear. We investigated the effect of SMG on host cell structure and mitochondrial functions and its impact on Toxoplasma gondii infection. Cultured human foreskin fibroblasts (HFF) and Vero cells under SMG formed stratified cell layers and exhibited morphological mitochondrial abnormalities, such as outer membrane distortion and inner membrane distension. Functional analyses revealed altered mitochondrial membrane potential and intracellular ATP levels without substantial changes in reactive oxygen species. Upon infection, T. gondii showed cell‐type‐dependent growth, increasing in Vero cells but decreasing in HFF at 48 h post‐infection. These findings indicate that SMG‐induced mitochondrial remodeling is associated with altered host cell susceptibility to toxoplasmosis. Our study highlights the role of physical environmental changes in modulating host–pathogen interactions in the context of host cell mitochondrial function.