FIRM
Financiado
Form and Function of the Mitochondrial Retrograde Response
The molecular communication between mitochondria and nucleus is an integrated bi-directional crosstalk - anterograde (nucleus to mitochondria) and retrograde (mitochondria to nucleus) signalling pathways. The mitochondrial retrogr...
The molecular communication between mitochondria and nucleus is an integrated bi-directional crosstalk - anterograde (nucleus to mitochondria) and retrograde (mitochondria to nucleus) signalling pathways. The mitochondrial retrograde response (MRR) is driven by defective mitochondrial function, which increases cytosolic reactive oxygen species (ROS) and Ca2+. Metabolic reprogramming is a key feature in highly proliferative cells to meet the energy needs for rapid growth by generating substrates for cellular biogenesis. In these mitochondria retro-communicate with the nucleus to induce wide-ranging cytoprotective effects exploited to develop resistance against treatment and sustain uncontrolled growth. Recently, the mitochondrial management of cholesterol-derived intermediates for the synthesis of steroids has been demonstrated as a determinant in the oncogenic reprogramming of cellular environment.
We hypothesise that cholesterol-enriched domains facilitate the communication between remodelled mitochondria and nucleus to expedite MRR. This mechanism may be exploited during abnormal cell growth in which cholesterol metabolism and associated molecules are increased.
This application capitalizes on expertise in cell signalling and metabolism to interrogate core pathways and unveil molecular sensors and effectors that define form and function of the MRR by:
I. Elucidating the mechanism of metabolic regulation of MRR, describing the role exerted by cholesterol trafficking;
II. Unveiling microdomains for mito-nuclear communication established by remodelled, autophagy escaped, mitochondria;
III. Validating protocols to modulate and target MRR for diagnostic and therapeutic benefit;
The experimental plan will (i) define a molecular signalling axis that currently stands uncharacterized, (ii) provide mechanistic knowledge for preventive, and (iii) therapeutic applications to counteract deficiencies associated with stressed, dysregulated mitochondria.
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Duración del proyecto: 84 meses
Fecha Inicio: 2019-03-13
Fecha Fin: 2026-03-31
Fecha Fin: 2026-03-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-03-13
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-COG:
ERC Consolidator Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
1M€
Líder del proyecto
QUEEN MARY UNIVERSITY OF LONDON
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
470.00K€ |
Participante