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UPRmt SIGNED

The Mitochondrial Unfolded Protein Response

Total Cost €

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EC-Contrib. €

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Partnership

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 UPRmt project word cloud

Explore the words cloud of the UPRmt project. It provides you a very rough idea of what is the project "UPRmt" about.

bacterial    exposes    mechanisms    energy    sense    mapping    mitonuclear    species    reference    encodes    genomes    function    networks    cytoplasm    clinically    genes    translating    genome    links    collected    times    subunits    imported    transmit    retained    life    vertebrates    therapies    rest    proteotoxic    oxphos    complexes    mitochondria    worms    phenotypes    association    proteins    harvesting    benefits    population    molecular    health    proteome    quality    human    critically    components    oxidative    mice    mechanistically    organelles    translated    invertebrates    genetic    lifespan    improves    induction    murine    clinical    regulatory    vestige    humans    endosymbiotic    integrating    stress    vivo    13    metabolism    elegans    phosphorylation    protein    mammalian    mtpqc    unfolded    cohorts    80    validating    proteobacteria    imbalance    cells    uprmt    inducers    specialized    encoded    influence    remaining    activating    dna    circuit    initially    gained    proteostasis    mitochondrial    nuclear    hits    circuits    re   

Project "UPRmt" data sheet

The following table provides information about the project.

Coordinator
ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE 

Organization address
address: BATIMENT CE 3316 STATION 1
city: LAUSANNE
postcode: 1015
website: www.epfl.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-11-01   to  2023-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE CH (LAUSANNE) coordinator 2˙500˙000.00

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 Project objective

Mitochondria—organelles specialized in energy harvesting through oxidative phosphorylation (Oxphos)—critically influence metabolism, health and lifespan. Evolved from endosymbiotic proteobacteria, mitochondria retained the vestige of the bacterial genome, the mitochondrial DNA, which encodes 13 subunits of the Oxphos complexes, while the remaining ~80 Oxphos components and the rest of the mitochondrial proteome are encoded on nuclear DNA, translated in the cytoplasm and imported in the mitochondria. The control of the mitochondrial proteome by two genomes exposes these organelles to proteotoxic stress in case of an imbalance between the nuclear- and mitochondrial-encoded proteins. Upon such stress, several mitochondrial protein quality control (mtPQC) pathways, including the mitochondrial unfolded protein response (UPRmt), will sense, transmit and re-establish mitochondrial proteostasis through mitonuclear regulatory circuits. Although a robust UPRmt circuit improves health and lifespan in C. elegans, much less is known about mtPQC in vertebrates. We propose here to characterize UPRmt pathways across 3 species by: (1) mapping mammalian UPRmt genes and networks in vivo after the induction of the UPRmt in a large murine genetic reference population at 3 different times throughout life with 2 different inducers; (2) integrating these UPRmt networks with a wide set of clinical, mitochondrial, and molecular phenotypes collected throughout life to establish links between UPRmt mechanisms and health- and lifespan; (3) mechanistically validating the most important UPRmt pathways, using loss-of-function studies in cells, worms and mice; and (4) clinically translating promising UPRmt hits, using genetic association studies in human cohorts. The insight gained will mechanistically define the UPRmt networks from worms to humans and will provide the next step in translating the benefits of activating the UPRmt—initially observed in invertebrates—into targeted human therapies.

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