Direct control of mitochondrial dynamics by regulatory amino acids

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***Almost every cell in our body contains hundreds of mitochondria that provide a range of essential functions including the generation of ATP. A truly fascinating hypothesis in biology is that mitochondria were once free-living bacteria, which became engulfed by a larger cell, to form a symbiotic relationship that survived evolution. Reflecting this bacterial origin, our mitochondria replicate by expansion of existing organelles followed by division (aka fission). Mitochondria also have the ability to join together (aka fusion) to form interconnected networks. We are now appreciating that fusion improves mitochondrial function in multiple ways, by decreasing DNA mutations, combining mitochondrial genomes and prevention of cell death. Better understanding of mitochondrial fusion and function could therefore lead to new strategies for tackling the slow decline of cell energetics and metabolism linked to aging. As we studied how cells respond to nutrient stress, we uncovered a novel pathway where amino acids stimulated strong mitochondrial hyperfusion. The responses cannot be explained by currently understood mechanism so here, we will study this mitochondrial remodelling and provide new fundamental knowledge that may impact many areas of biology and medicine. The transport pathways that allow mitochondria to sense amino acids are not well understood, despite the fact that mitochondria rely on a range of these nutrients. Since this represented a key question in biology that needed further detail, we chose to explore this area using our system. We will determine how amino acids and hyperfusion help support higher levels of metabolism within the mitochondria. Lastly, to allow control of this pathway, we need to understand the regulatory mechanisms so we will define the cell signalling patterns that drive nutrient-dependent mitochondrial fusion. To address these questions, we will train a group of HQP who gain experience using high-powered techniques in cell biology including CRISPR gene-targeting, metabolomics and phosphoproteomics. Our research program here will contribute a new area on nutrient sensing to the mitochondrial biology research community in Canada.