Mitochondria of a human skeletal muscle cell line associate with the parasitophorous vacuoles of three archetypal lineages of Toxoplasma gondii and influence fatty acid import.

Abstract

Toxoplasma gondii, an obligate intracellular parasite, acquires host nutrients to sustain its intracellular replication. A key interaction involves host mitochondrial association (HMA) with the parasitophorous vacuole membrane, previously thought to be strain- and cell-type-dependent, and notably absent in type 2 strains in fibroblasts. Here, we report that in human skeletal muscle KD3 myotubes, all three archetypal T. gondii strains-including type 2-demonstrate significant HMA. This association was confirmed by mitotracker staining and transmission electron microscopy. Notably, HMA appears to correlate inversely with the parasite's uptake of exogenous ¹³C-labeled fatty acids, suggesting a competitive nutrient environment shaped by host mitochondrial proximity. These findings highlight host cell-type specificity in mitochondrial interactions and suggest that HMA may function as a modulator of nutrient acquisition in a context-dependent manner. This work revises the understanding of strain-specific HMA and underscores the complexity of host-parasite metabolic interactions in muscle tissue, a physiologically relevant niche for chronic T. gondii infection.