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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.

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

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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