There are hundreds of mitochondria inside each cell working as combustion engines. They use the oxygen that we breath to burn fat and sugar, and the energy derived from this is used as fuel for our bodies. We have long assumed that these cellular furnaces sit idly within the cell, doing their work without much attention to the general state of the cell. Recent data has changed this view, since we have realized that they are extremely dynamic structures, fusing together, branching and splitting into pieces. Our lab takes a number of complementary approaches to try and understand why the mitochondria behave as an interconnected group, and what this means to the cell, the tissue, and the body. Importantly, mutations in mitochondrial shape-shifting proteins lead to serious degenerative diseases, and the plasticity of these organelles is tied directly to clearing away damaged sections of protein and lipid. Mitochondrial dysfunction is now causally linked to ALS, Parkinson’s Disease, and others, which has led to my recruitment to the Neuro. We hope that by characterizing the details of mitochondrial behavior, that we will identify new therapeutic approaches to treating degenerative disease. Operating within the Rare Neurological Disease Group, I am part of a multidisciplinary team, contributing an expertise in the cell biology of mitochondrial dysfunction to the complex pathogenesis of motorneuron and other degenerative diseases.
Scientific outline of research
We focus on three core aspects of mitochondrial function:
- The mechanism and function of mitochondrial fusion. Using biochemical and imaging approaches, we are searching for the detailed mechanisms to explain how two mitochondria, each with two membranes, manage to fuse together and mix their contents. The consequences of this process going wrong are evident in human patients with mutations in the fusion proteins, so we hope that by expanding our understanding at the molecular level, we may contribute to more targeted therapeutic strategies
- The role of SUMOylation in mitochondrial fission and intracellular signaling. The Small Ubiquitin-like Modifier protein SUMO can be covalentatly conjugated to target proteins in a post-translational modification that alters protein function, localization and sometimes turnover. We have been studying the role of SUMOylation on the mitochondria, how it functions during mitochondrial fission, during cell death, cell division, using a variety of approaches. We are working to solve the mitochondrial SUMO proteome, and there are a number of surprises lying ahead
- Characterization of mitochondrial derived vesicles. We have discovered that the mitochondria are able to sort specific protein and lipid cargo into small vesicular carriers that are delivered to distinct intracellular compartments. This opens entirely new avenues of research into what controls the formation of these vesicles, how they are transported, and what are the consequences when these pathways fail. The relationship of these vesicles to mitochondrial health in neurons will be of great interest to us in the coming years at the Neuro
This research is currently funded by the CIHR (MOPs#68833 and 123398),and HMM is supported by a Canada Research Chair (Tier 1).
Past funding includes the Canadian Research Society Innovation Grant, Juvenile Diabetes Research Foundation (JDRF), Heart and Stroke Foundation of Ontario (HSFO), and Neuroscience Canada’s Brain Repair Program.