弓形虫Coq4氧化脱羧酶在辅酶Q生物合成和线粒体功能中的作用研究

Abstract

As an obligate intracellular parasite, Toxoplasma gondii is a widely distributed zoonotic pathogen posing a substantial threat to both human and animal health. Interestingly, T. gondii contains only a single and divergent mitochondrion that supports its metabolism and rapid proliferation. Coenzyme Q (CoQ), a lipid-soluble electron carrier, is essential for mitochondrial electron transport, cellular energy metabolism, and redox homeostasis. CoQ biosynthesis involves a series of enzymatic reactions, and its key proteins have been identified and functionally characterized in various eukaryotes. However, the functions of CoQ biosynthetic proteins in T. gondii remain poorly understood. In this study, we identified TgCoq4 as a conserved component protein of the CoQ biosynthetic pathway in T. gondii , and confirmed that it displays oxidative decarboxylation activity. Genetic depletion of TgCoq4 leads to impaired parasite growth, accompanied by mitochondrial structural damage and functional deficiency. In addition, TurboID-based proximity labeling technology combined with mass spectrometry analysis confirmed that TgCoq4 is spatially associated with multiple CoQ biosynthetic proteins. Therefore, this study identifies TgCoq4 as a key component of CoQ biosynthesis and provides new insights into mitochondrial mechanism in T. gondii .