The Role of Complex I Assembly Factors during Prion Diseases: Insights into Mitochondrial Neurobiology

Información del proyecto

Prion Respiration

Identificador del acuerdo de subvención: 844194

DOI

10.3030/844194

Proyecto finalizado el 31 Agosto 2020

Fecha de la firma de la CE 9 Abril 2019

Fecha de inicio 1 Octubre 2019

Fecha de finalización 30 Septiembre 2021

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 171 473,28

Aportación de la UE

€ 171 473,28

Coordinado por

UNIVERSITA DEGLI STUDI DI TRENTO
Italy

Objetivo

Mitochondria have a crucial role in cell survival and apoptosis, in particular in long-lived cells such as neurons. Mitochondria generate energetic potential through respiratory complexes I to IV, which constitute the electron transport chain. A number of studies demonstrates that mitochondrial integrity declines as a function of aging and dysfunctions may be exacerbated by age-related neurodegenerative diseases. Altered levels of complex I proteins have been found to be directly responsible for a decrease in energy production in Alzheimer’s and Parkinson's disease. Recently, a number of nuclear encoded mitochondrial proteins, denoted as “assembly factors” (AFs), have been identified as crucial components helping the complex I assembly. Defects in AFs (due to mutations or aberrant AFs processing) may cause complex I misassembly and mitochondrial dysfunctions leading to a broad spectrum of diseases, including neurological disorders in childhood-related dieseas as Leigh syndrome. The functional role of AFs during neurodegeneration has not been investigated yet. With the “Prion Respiration” project I propose to develop a research approach aimed at the identification of the biological role of three crucial complex I AFs (namely ECSIT, NDUFAF1 and ACAD9) in cellular and animal models using prion diseases as robust system to study neurodegenerative diseases. Subsequently, the role of prions in interfering the with the correct assembly of the AFs will be investigated using structural biology approaches, as SAXS and cryo-EM methods. The structural and functional characterization of key proteins involved in mitochondrial respiration will provide insights into the underlying mechanisms involved in neuronal function and may represent novel targets for structure-based drug design strategies to prevent or diminish the oxidative stresses underlying neurodegeneration.

Ámbito científico (EuroSciVoc)

• ciencias naturales › ciencias biológicas › neurobiología
• ciencias médicas y de la salud › medicina básica › neurología › demencia › alzheimer
• ciencias médicas y de la salud › medicina básica › química medicinal
• ciencias médicas y de la salud › medicina básica › neurología › parkinson
• ciencias naturales › ciencias biológicas › biología molecular › biología estructural

Palabras clave

• Mitochondria
• respiratory Complex I
• neurodegeneration
• prion diseases
• prions
• Complex I assembly
• factors
• MCIA complex
• Complex I assembly
• transgenic mice
• CRISPR CAS9
• mitochondrial
• neurobiology

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2018 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2018

Coordinador

UNIVERSITA DEGLI STUDI DI TRENTO

• Aportación neta de la UEn: € 171 473,28
• Dirección: VIA CALEPINA 14 ; 38122 TRENTO ; Italia
• Región: Nord-Est › Provincia Autonoma di Trento › Trento
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 171 473,28