Heidi McBride

Bio

As a member of a multidisciplinary team, Heidi McBride contributes her expertise in the cell biology of mitochondrial dysfunction to the complex pathogenesis of motor neuron and other degenerative diseases. Her laboratory uses various complementary approaches to try to understand why hundreds of mitochondria inside each cell behave as an interconnected group, and what this interaction means to the cell, to tissues and to the body. Mitochondria work as combustion engines, using oxygen to burn fat and sugar. The consequent energy is used in our bodies as fuel. It was long thought that mitochondria performed their function without disturbing the general state of the cell, but recent data has changed this view. Today, mitochondria are seen as extremely dynamic structures that fuse together, branch and split apart.

Mutations in mitochondrial proteins can lead to serious degenerative diseases. The plasticity of these organelles is tied directly to removing damaged sections of protein and lipid. Mitochondrial dysfunction is now linked to the causes of diseases such as Amyotrophic Lateral Sclerosis and Parkinson’s disease. By characterizing mitochondrial behaviour, McBride hopes to identify new therapeutic approaches to treating degenerative disease.

McBride’s laboratory focuses on three aspects of mitochondrial function. Mitochondrial fusion: The mechanisms to explain how two mitochondria, each with two membranes, can fuse and mix their content. It has been shown that mutations in proteins that regulate mitochondrial fusion lead to a series of neurodegenerative diseases. By expanding our understanding of this process at the molecular level, McBride hopes to contribute to more targeted therapeutic strategies.

Role of SUMOylation in mitochondrial fission and intracellular signaling: The Small Ubiquitin-like Modifier protein, SUMO, can be covalently conjugated to target proteins in a post-translational modification that alters protein function, localization and sometimes turnover. McBride’s laboratory uses various approaches to study how SUMOylation functions during mitochondrial fission, cell death and cell division.

Characterization of mitochondrial-derived vesicles: McBride’s research found that mitochondria can sort specific protein and lipid cargo into small vesicular carriers, which are delivered to distinct intracellular compartments. This discovery opens new avenues into examining the mechanisms that control these vesicles’ formation and transport, as well as into the consequences of pathway failure.