Versatility of sterol biosynthesis during the lifecycle in a close unicellular relative of animals

SEBASTIÁN R. NAJLE; MARÍA CELESTE MOLINA; ANTONIO D. UTTARO

Rosario

Jornada; L Reunión Anual de la SAIB; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Sterols are essential for several physiological processes in eukaryotes. Here, we provide strong genetic and biochemical evidence about the biphasic nature of the sterols metabolism in Capsaspora owczarzaki, a close unicellular relative of metazoans. The life cycle of C. owczarzaki presents an amoeboid stage, a multicellular aggregative stage and a cystic stage, assumed as a resistance form. The C. owczarzaki genome shows the presence of a complete set of genes for the canonical biosynthesis pathway of ergosterol, the typical sterol of Fungi, as well as the presence of an ortholog of the Rieske sterol C7(8)-desaturase, previously described by our group in the unrelated ciliate species Tetrahymena thermophila. However, the sterols profile obtained by GC/MS suggests the cells are able to convert exogenous cholesterol into ergosterol by using a novel pathway. This was further confirmed by supplementation studies with radioactive precursors. Moreover, we demonstrate the lack of de novo sterol synthesis during the amoeboid and aggregative stages. Nevertheless, we were able to detect de novo produced 7-dehydrocholesterol in the cystic stage. Conversion of cholesterol into ergosterol involves the action of three enzymes from the ergosterol canonical pathway, as well as the sterol C7(8)-desaturase. These findings are supported by available transcriptomics data of the C. owczarzaki lifecycle.