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The HSP90 paralog TRAP1 oligomerizes into an OXPHOSregulated protein complex that may be essential for maintaining mitochondrial metabolic homeostasis

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Defense Thèse de doctorat : Univ. Genève, 2019 - Sc. Vie 28 - 2019/08/27
Abstract The molecular chaperone TRAP1 has been studied for almost two decades, yet, the mechanistic basis underlying its function in the mitochondria still remains poorly understood. Recent studies have presented it as an inhibitor of OXPHOS and an inducer of the Warburg phenotype, but multiple reports have conflicted with this paradigm. This study seeks to reconcile previous reports in a cohesive model by proposing that TRAP1 does not necessarily down or upregulate OXPHOS, but, is actually required to maintain OXPHOS homeostasis. Using multiple CRISPR KO cell lines, real time OCR analyses with different carbon sources, metabolomics and various proteomic approaches to understand interactions, this study provides a platform to understand TRAP1 function in mitochondria. We show that TRAP1 induces a metabolic rewiring independent of its ATPase activity, requires an ATP-bound state to interact with various mitochondrial proteins and forms an oligomerized protein complex that may be the functional unit of TRAP1.
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URN: urn:nbn:ch:unige-1231658
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Research group Groupe Picard
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JOSHI, Abhinav. The HSP90 paralog TRAP1 oligomerizes into an OXPHOSregulated protein complex that may be essential for maintaining mitochondrial metabolic homeostasis. Université de Genève. Thèse, 2019. doi: 10.13097/archive-ouverte/unige:123165 https://archive-ouverte.unige.ch/unige:123165

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Deposited on : 2019-09-16

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