Skip to main content
Go to the home page of the European Commission (opens in new window)
English en
CORDIS - EU research results
CORDIS

Mitochondrial Contact Site Functional Diversity Revealed by Molecular Memory, Smart Microscopy, and Correlative Cryo-EM Tomography

Project description

How membrane contact sites coordinate mitochondrial function

Mitochondria are essential to complex life, supplying energy while carefully regulating their own growth inside the cell. They communicate with other organelles through brief points of contact that allow signals and molecules to pass between them. These fleeting connections are crucial to cell health, but their short-lived nature makes them difficult to observe. The ERC-funded MitoContact project aims to explore MCS using chemical biology recorders and live-cell smart microscopy. It will study how these contacts coordinate mitochondrial function and physiology. By focusing on key interactions in mitochondrial dynamics, the project seeks to identify MCS inhibitors or stabilisers, potentially impacting therapeutics and broader biological discoveries.

Objective

Mitochondria are central to modern eukaryotic life, but how they carry out their functions in space and time within the cellular milieu is remarkably enigmatic. Contributing to the complexity of this question, mitochondria face dual existential challenges: supporting their life cycle as self-reproducing, DNA-containing organelles; and supporting the energetic and signaling needs of the host cell. A universal feature in how mitochondria address these challenges is via engagement in membrane contact sites (MCS) - sites of intracellular signaling or biomolecular exchange - with partner organelles. Candidate MCS proteins between partners range into the hundreds, driving speculation that diverse contacts exist. However, technological limitations in measuring the composition, structure, dynamics and physiology of transient MCS have hindered progress in dissecting their functional diversity.

Our project will develop and apply cutting-edge technologies to investigate the dynamics and molecular organization of MCS, to reveal how individual contacts locally coordinate mitochondrial physiology and function. We will deploy (1) chemical biology “recorders,” enabling us to trace the history of MCS and physiology. We will combine this with (2) live-cell “smart microscopy,” driven by closed-loop feedback through real time neural-network recognition of cellular events, to capture dynamics with high specificity and spatio-temporal resolution and (3) cellular cryo-correlative microscopy to obtain structural snapshots and gain insights into MCS molecular architecture. We will focus on heterotypic and homotypic contacts implicated in mitochondrial proliferation, degradation, molecular exchange, and metabolic states. Our synergistic approach will allow us to screen for MCS inhibitors or stabilizers and measure the impact of disrupting contacts. Thus, we expect our project to have broader implications for therapeutics, and our tools to impact fundamental biological discovery beyond MCS.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

See all projects funded under this funding scheme

Call for proposal

(opens in new window) ERC-2025-SyG

See all projects funded under this call

Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Net EU contribution
€ 5 321 878,00
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland
Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 5 321 878,00

Beneficiaries (3)