Exploration of the Architecture and Functional Relevance of Mammalian Dolichol Synthesis

Details

Supervisors

Bommer, Guido ; Siviero, Francesca

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

enDolichol is a polyisoprenoid embedded in the membrane of the endoplasmic reticulum and is involved in protein N-glycosylation which is essential for proper protein folding, trafficking and function. Deficiencies in dolichol synthesis disrupt N-glycan formation, resulting in congenital disorders of glycosylation (CDG). Dolichol was previously thought to derive directly from polyprenol via a single reduction step catalysed by SRD5A3. However, recent findings from my laboratory revealed a revised synthesis pathway involving three reactions that include a second enzyme, DHRSX, and two intermediates, polyprenal and dolichal. My master’s thesis aims to understand the architecture of cellular dolichol metabolism and explore how disturbances can contribute in human pathologies. To achieve this we used proximity-labelling techniques to better characterize subcellular localization and interaction networks of DHRSX and SRD5A3. Future studies will be needed to understand the interaction partners that we identified, as well as the mechanisms by which abnormal products of dolichol biosynthesis may lead to human disease.