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RevMito SIGNED

Deciphering and reversing the consequences of mitochondrial DNA damage

Total Cost €

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EC-Contrib. €

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Partnership

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Project "RevMito" data sheet

The following table provides information about the project.

Coordinator
HELSINGIN YLIOPISTO 

Organization address
address: YLIOPISTONKATU 3
city: HELSINGIN YLIOPISTO
postcode: 14
website: www.helsinki.fi

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 Finland [FI]
 Project website http://www.biocenter.helsinki.fi/bi/dunn/lab/DunnLab/
 Total cost 1˙497˙160 €
 EC max contribution 1˙497˙160 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2020-03-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELSINGIN YLIOPISTO FI (HELSINGIN YLIOPISTO) coordinator 1˙033˙640.00
2    KOC UNIVERSITY TR (ISTANBUL) participant 463˙519.00

Map

 Project objective

Mitochondrial DNA (mtDNA) encodes several proteins playing key roles in bioenergetics. Pathological mutations of mtDNA can be inherited or may accumulate following treatment for viral infections or cancer. Furthermore, many organisms, including humans, accumulate significant mtDNA damage during their lifespan, and it is therefore possible that mtDNA mutations can promote the aging process.

There are no effective treatments for most diseases caused by mtDNA mutation. An understanding of the cellular consequences of mtDNA damage is clearly imperative. Toward this goal, we use the budding yeast Saccharomyces cerevisiae as a cellular model of mitochondrial dysfunction. Genetic manipulation and biochemical study of this organism is easily achieved, and many proteins and processes important for mitochondrial biogenesis were first uncovered and best characterized using this experimental system. Importantly, current evidence suggests that processes required for survival of cells lacking a mitochondrial genome are widely conserved between yeast and other organisms, making likely the application of our findings to human health.

We will study the repercussions of mtDNA damage by three different strategies. First, we will investigate the link between a conserved, nutrient-sensitive signalling pathway and the outcome of mtDNA loss, since much recent evidence points to modulation of such pathways as a potential approach to increase the fitness of cells with mtDNA damage. Second, we will explore the possibility that defects in cytosolic proteostasis are precipitated by mtDNA mutation. Third, we will apply the knowledge and concepts gained in S. cerevisiae to both candidate-based and unbiased searches for genes that determine the aftermath of severe mtDNA damage in human cells. Beyond the mechanistic knowledge of mitochondrial dysfunction that will emerge from this project, we expect to identify new avenues toward the treatment of mitochondrial disease.

 Publications

year authors and title journal last update
List of publications.
2019 Michal Eisenberg-Bord, Hui S. Tsui, Diana Antunes, Lucía Fernández-del-Río, Michelle C. Bradley, Cory D. Dunn, Theresa P. T. Nguyen, Doron Rapaport, Catherine F. Clarke, Maya Schuldiner
The Endoplasmic Reticulum-Mitochondria Encounter Structure Complex Coordinates Coenzyme Q Biosynthesis
published pages: 251525641882540, ISSN: 2515-2564, DOI: 10.1177/2515256418825409
Contact 2 2020-03-31
2019 Oygul Mirzalieva, Shinhye Jeon, Kevin Damri, Ruth Hartke, Layla Drwesh, Keren Demishtein-Zohary, Abdussalam Azem, Cory D. Dunn, Pablo M. Peixoto
Deletion of Mgr2p Affects the Gating Behavior of the TIM23 Complex
published pages: , ISSN: 1664-042X, DOI: 10.3389/fphys.2018.01960
Frontiers in Physiology 9 2020-03-31
2016 Emel Akdoğan, Mehmet Tardu, Görkem Garipler, Gülkız Baytek, İ. Halil Kavakli, Cory D. Dunn
Reduced Glucose Sensation Can Increase the Fitness of Saccharomyces cerevisiae Lacking Mitochondrial DNA
published pages: e0146511, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0146511
PLOS ONE 11/1 2019-05-29
2017 Cory D. Dunn
Some Liked It Hot: A Hypothesis Regarding Establishment of the Proto-Mitochondrial Endosymbiont During Eukaryogenesis
published pages: 99-106, ISSN: 0022-2844, DOI: 10.1007/s00239-017-9809-5
Journal of Molecular Evolution 85/3-4 2019-05-29
2017 Abdurrahman Keskin, Emel AkdoÄŸan, Cory D. Dunn
Evidence for Amino Acid Snorkeling from a High-Resolution, In Vivo Analysis of Fis1 Tail-Anchor Insertion at the Mitochondrial Outer Membrane
published pages: 691-705, ISSN: 0016-6731, DOI: 10.1534/genetics.116.196428
Genetics 205/2 2019-05-29
2017 Güleycan Lutfullahoğlu-Bal, Abdurrahman Keskin, Ayşe Bengisu Seferoğlu, Cory D. Dunn
Bacterial tail anchors can target to the mitochondrial outer membrane
published pages: , ISSN: 1745-6150, DOI: 10.1186/s13062-017-0187-0
Biology Direct 12/1 2019-05-29
2018 Güleycan Lutfullahoğlu-Bal, Ayşe Bengisu Seferoğlu, Abdurrahman Keskin, Emel Akdoğan, Cory D. Dunn
A bacteria-derived tail anchor localizes to peroxisomes in yeast and mammalian cells
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-34646-7
Scientific Reports 8/1 2019-05-22

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