MITOCHONTACTS · Mitochondrial membrane contact sites
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2016-05-01 → 2018-04-30
- EU contribution
- €182,509
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Mitochondrial membrane contact sites
Our body works like a commune. The multitude of tasks our body has to meet are performed in coordination between distinct organs such as the heart, the liver and the brain. This principle of division of labor goes down to the smallest living unit in our body, the cell. We have 50 trillion cells in our bodies and they each perform many functions. Different functions that a cell has to fulfill are carried out by intracellular structures termed organelles. For example, mitochondria function as the power plants of the cell, and lipid droplets are energy storehouses. The inside of each organelle is protected by a surrounding membrane. The presence of organelles has numerous benefits for the cell. They offer separate cellular reaction chambers and thus allow for the cell to perform diverse functions at the same time, even functions that are conflicting with each other or that require different environmental conditions. On the down-side however, maintaining organelles also comes at a cost. For example, organelles require an elaborate communication system in order for the cell to function in coordination. One key way of organelle communication is via contact sites, places where two organelles are physically linked to each other via special proteins that are spanning the membranes of both organelles. They key objective of this project was to gain a deeper understanding about the molecules underlying formation of contact sites, their functional roles, and their relevance for the cell.
Data: CORDIS, © European Union
Project objective
Organelles offer separate reaction chambers within a eukaryotic cell, thus expanding cellular metabolic capacity but necessitating mechanisms for interorganellar communication. Mitochondria are key players in cellular metabolism and their dysfunction leads to devastating conditions. Intriguingly, they are largely excluded from vesicular trafficking, creating a mystery of how they can fulfill their functions despite being cut off from these important routes of intracellular crosstalk. Membrane contact sites (CS) are starting to be appreciated as a further, vesicle independent, means of communication between organelles. CS are domains where membranes of distinct organelles are tethered by proteinaceous machineries. Factors tethering mitochondria to the endoplasmic reticulum, the vacuole/lysosome and the plasma membrane are known. Electron microscopy studies suggest existence of several additional mitochondrial CS that are currently unknown at a molecular level. Discovery of the principle of interorganellar crosstalk via CS finally offers a solution to the paradox of mitochondria as metabolic hubs being largely excluded from vesicular traffic. In order to understand how mitochondria are integrated into cellular physiology, we need to know the molecular nature of the entire repertoire of CS, their specific biological roles and their regulation in response to metabolic changes. I will utilize a systematic approach to map the complete spectrum of CS between mitochondria and any other cellular organelle in the most experimentally accessible eukaryotic model organism, the yeast Saccharomyces cerevisiae. My approach relies on creation of a molecular sensor for contact sites and its utilization in high content screens to uncover the tethers, regulators and function of mitochondrial CS. Ultimately, my goal is to build a model describing the integration of mitochondrial behavior into cellular physiology via CS-based mechanisms on a holistic level.
Original text from CORDIS.
Participants
- WEIZMANN INSTITUTE OF SCIENCE · RehovotCoordinatorIsrael
Links
Data: CORDIS, © European Union