Cytotoxicity of neuropathy-causing lipids 1-deoxy-sphingolipids

Diplôme Thèse Cytotoxicity of neuropathy-causing lipids 1-deoxy-sphingolipids eng 2018-05-03 author Galih Augustinus 793135 director Riezman Howard 134430 10.13097/archive-ouverte/unige:104519 urn:nbn:ch:unige-1045192 Sc. 5207 Hereditary sensory and autonomic neuropathy type IA and IC (HSAN IA/IC) are caused by autosomal dominant mutations that lead to the accumulation of atypical lipids called 1-deoxy-sphingolipids. How the lipids perturb the physiology of the cell are largely unknown. By combining genetics, lipidomics, and chemical proteomics approaches in the budding yeast, our study showed that there are two sequential and overlapping events in the cell. The first event comprises perturbations of actin organization, alteration of the shape of mitochondria, and formation of hydrophobic bodies by 1-deoxy-sphinganine. These aberrations, however, are not sufficient to kill the cell. The second event is the toxicity of C26 1-deoxy-ceramide. The lipid might directly inhibit a multisubunit essential protein that has broad impacts, directly inhibit multiple essential proteins, or perturb the structure of cellular membranes. Each of these perturbations is sufficient to kill the cell. Hereditary sensory and autonomic neuropathy HSAN 1-deoxy-sphingolipid Budding yeast Dewey 540 39 Département de biochimie 144 false 768 Groupe Riezman c8966ea0-0b47-451e-b60e-ebdeb167a64e Thesis Public ThesisofAugustinusGalih.pdf 3314497 application/pdf Private 2019-05-14 e24b7881e9af8bf77bfe27b0f65c5615f542ef170cfb5cbfad5b9b5063d77f59 openAccess Faculté des sciences / Section de chimie et biochimie / Département de biochimie

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Cytotoxicity of neuropathy-causing lipids 1-deoxy-sphingolipids				2018	667	209

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Galih, Augustinus