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

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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