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Cytotoxicity of neuropathy-causing lipids 1-deoxy-sphingolipids

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Defense Thèse de doctorat : Univ. Genève, 2018 - Sc. 5207 - 2018/05/03
Abstract 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.
Keywords Hereditary sensory and autonomic neuropathyHSAN1-deoxy-sphingolipidBudding yeast
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URN: urn:nbn:ch:unige-1045192
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Research group Groupe Riezman
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GALIH, Augustinus. Cytotoxicity of neuropathy-causing lipids 1-deoxy-sphingolipids. Université de Genève. Thèse, 2018. https://archive-ouverte.unige.ch/unige:104519

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Deposited on : 2018-05-16

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