The Neuro Team

As a member of a multidisciplinary team, Dr. 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, Dr. McBride hopes to identify new therapeutic approaches to treating degenerative disease.

Dr. 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, Dr. 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. Dr. McBride's laboratory uses various approaches to study how SUMOylation functions during mitochondrial fission, cell death and cell division.

Characterization of mitochondrial-derived vesicles: Dr. 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.

Web Site: McBride Lab

Publications:

Braschi, E., Goyon, V., Zunino, R., Mohanty, A., Xu, L. and McBride, H.M. Vps35 mediates vesicle transport between the mitochondria and peroxisomes. Current Biology, 20(14):1310-5, 2010. HSFO 5769.

Schauss, A.C., Huang, H., Choi, S-Y, Xu, L., Bilodeau, P., Zunino, R., Rippstein, P., Frohman, M.A., and McBride, H.M. A novel cell-free mitochondrial fusion assay demonstrates regulation through intracellular signaling cascades. BMC Biology Jul 26;8:100, 2010. CIHR 43935.

Braschi, E., Zunino, R., and McBride, H.M. MAPL is a novel mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Reports, 10(7):748-54, 2009. CIHR 68833.

Andrade-Navarro, M.A., Sanchez-Pulido, L., and McBride, H.M. Mitochondrial vesicles: an ancient process providing new links to peroxisomes. Current Opinion in Cell Biology; 21(4):560-7, 2009

Zunino, R., Braschi, E., Xu, L., and McBride, H.M. Translocation of SenP5 from the nucleoli to the mitochondria modulates DRP1 dependent fission during mitosis. Journal of Biological Chem. 284(26):17783-95, 2009. CIHR 68833

Soubannier, V. and McBride H.M. Positioning mitochondrial plasticity within cellular signaling cascades. Biochem. Biophys. Acta (Molecular Cell Biology), 1793(1):154-70, 2009 review.

McBride, H.M. Parkin mitochondria in the autophagosome. Journal of Cell Biol. 183, 757-759, 2008. Invited commentary.

Neuspiel, M., Schauss, A.C., Braschi, E., Zunino, R., Rippstein, P., Rachubinski, R.A., Andrade-Navarro, M.A., and McBride, H.M. Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers. Current Biology. 18(2), 102-108, 2008. HSFO 5769

Poole, AC, Thomas, RE, Andrews, LA, McBride, HM, Whitworth, AJ, Pallanck, LJ.

The PINK1/Parkin pathway regulates mitochondrial morphology. PNAS (Track II) 105(5), 1638-1643, 2008. Neuro BRP

Wasiak, S., Zunino, R. and McBride, H.M. Bax/Bak promote SUMOylation of DRP1 and its stable association with mitochondria during apoptotic cell death. Journal of Cell Biology. 177: 439-450, 2007 CIHR 68833

Zunino, R., Rippstein, P., Andrade-Navarro, M., and McBride, H.M. The SUMO protease SenP5 is required to maintain mitochondrial morphology and function. Journal of Cell Science, 120(7):1178-1188, 2007 CIHR 68833

Schauss, A,C. and McBride, H.M. Mitochondrial Fission: A Non-Nuclear Role for Num1p Current Biology Vol 17, R467-R470, 2007 (Dispatch). CIHR 68833

Cheung, E., McBride, H.M., and Slack, R. Mitochondrial dynamics in the regulation of neuronal cell death. Apoptosis. 12(5): 979-992, 2007