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INTEGRATE

Financiado

Intramitochondrial seeding and sorting of protein aggregates

Quality control processes maintain mitochondrial health, enabling cellular functions such as bioenergetics, metabolism, Ca2+ signaling, and cell death regulation. Mitochondrial proteases, unfolded protein response, asymmetric fiss... ver más

31/05/2029

UNIPD

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITA DEGLI STUDI DI PADOVA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-15

ERC-2023-ADG: ERC ADVANCED GRANTS Scope:Objectives

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Cerrada hace 1 año

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UNIPD

2.50M€ | Lider

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Duración del proyecto: 60 meses Fecha Inicio: 2024-05-15
Fecha Fin: 2029-05-31

Líder del proyecto

UNIVERSITA DEGLI STUDI DI PADOVA No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Quality control processes maintain mitochondrial health, enabling cellular functions such as bioenergetics, metabolism, Ca2+ signaling, and cell death regulation. Mitochondrial proteases, unfolded protein response, asymmetric fission, vesicle shedding, and mitophagy all contribute to organelle quality. However, the specific triggers for these processes remain unclear. While unfolded protein accumulation appears to be a common trigger, the mechanism by which it initiates diverse responses remains uncertain. To investigate this question, we developed advanced tools for real-time imaging of protein aggregation in mitochondrial subcompartments. Aggregates in the matrix and intermembrane space induce mitochondrial fission and elicit distinct functional responses based on their location. Live imaging revealed that intermembrane space aggregates initially seed in the mitochondrial midzone and then sort through transient side-by-side fusion with neighboring mitochondria. In the matrix, aggregates seed at one pole and are selectively sorted to daughter mitochondria through asymmetric fission. Our preliminary experiments unveiled an early seeding and sorting process of protein aggregates according to their intramitochondrial location. In the INTEGRATE project, we aim to comprehensively understand the underlying principles and consequences of this process. By combining advanced imaging techniques, omics analysis, biochemistry, functional assays, and unbiased screenings, we will decipher the rules governing aggregate formation, seeding, sorting, cellular fate, and response in various mitochondrial subcompartments. INTEGRATE seeks to establish the occurrence and downstream responses of this newly discovered early phase of mitochondrial quality control. Clarifying this fundamental mechanism will provide insights into mitochondrial and cell biology, with significant implications for pathological conditions and aging, where mitochondrial quality control is compromised.

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