Research

Mitochondria in cell communication

Cancer is a complex and heterogenous disease composed by several cell types including fibroblasts, immune cells and vascular and lymphatic endothelial cells. All of these cell types form the tumor microenvironment.  The communication between all of those cells favors tumor growth and metastasis spread.

Picture representing the tumor microenvironment (TME). CAF: Cancer associated fibroblasts. EC: Endothelial cells. IC: Immune cells.

We have recently shown the importance of mitochondrial network integrity in vascular and lymphatic endothelial cells to enhance the tumor growth and metastasis spread (Herkenne et al.; Cell Metabolism, 2020).

This work highlights that mitochondria play a key role in cell communication and opens important question about the role of host organelles and metabolism in the execution of signal during cell-to-cell communication.  Using endothelial cells and tumor cell as a model of cell-to-cell communication we will ask:

How do mitochondria regulate intracellular communication?

We have defined a regulated interaction between mitochondria and endosomes in endothelial cells, but we know nothing about the signals that enable mitochondria to sense and metabolically acts on endosomes. We seek to understand the pathways that orchestrate how these organelles interacts upon endothelial stimuli and define what role they play in the cellular trafficking.

Confocal microscopy Endosomes (green) and mitochondria (red).

How do mitochondria control cell-to-cell communication?

If mitochondria control the intracellular trafficking, one logical prediction would be that host mitochondria and metabolism is actively involved as part of the cell-to-cell communication. Indeed, a way of communication between different cell types is trough extracellular vesicles. Extracellular vesicles originate from endosomal compartment from mutivesicular bodies.  So far, the mechanism of extracellular vesicles secretion is still poorly understood. We will define the mitochondrial and metabolic pathways that impact in the extracellular vesicles secretion and dissect how the metabolism rewiring modulates extracellular vesicles rewiring.

Confocal Images of mitochondria (green) and multivesicular bodies (red) in control cells and upon mitochondria fragmentation.