Heidi McBride, PhD
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.
Matheoud, D., Sugiura, A., Bellemare-Pelletier, A., Laplante, A., Rondeau, C., Chemali, M., Fazel, A., Bergeron, JJ, Trudeau, LE, Burelle, Y., Gagnon, E., McBride, HM*, Desjardins, M*., Parkinson’s Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation. Cell 2016 DOI: https://www.sciencedirect.com/science/article/pii/S0092867416305906?via%3Dihub (*co-corresponding authors). CIHR133549
Cadete, VJ, Deschênes, S., Cuillerier, A., Brisebois, F., Sugiura, A., Vincent, A., Turnbull, D., Picard, M., McBride, H., Burelle, Y. Formation of Mitchondrial-derived vesicles is an active and physiologically relevant mitochondrial quality control process in the cardiac system. J Physiol. 2016 Jun 17. doi: 10.1113/JP272703. CIHR133549
Prudent J*, Zunino R*, Sugiura A*, Mattie S*, Shore GC, McBride HM. MAPL SUMOylation of Drp1 Stabilizes an ER/Mitochondrial Platform Required for Cell Death. Mol Cell. 2015 Sep 17;59(6):941-55. CIHR68833, CCSRI
McBride HM. Open questions: seeking a holistic approach for mitochondrial research. BMC Biol. 2015 Feb 5;13(1):8.
Sugiura A*, McLelland GL, Fon EA, McBride HM. A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. 2014 Oct 1;33(19):2142-2156. (Review) CIHR133549
Norton M, Ng AC, Baird S, Dumoulin A, Shutt T*, Mah N, Andrade-Navarro MA, McBride HM, Screaton RA. ROMO1 Is an Essential Redox-Dependent Regulator of Mitochondrial Dynamics. Sci Signal. 2014 Jan 28;7(310):ra10. CIHR43935
*Article chosen for “Perspective” in Sci. Signal. 7 (310), pe2, 2014
McLelland GL, Soubannier V*, Chen CX, McBride HM*, Fon EA. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014 Jan 20. (*co-corresponding author) HSFO 5769 and BRP
*Article highlighted as “Editor’s Choice” in Science vol 343, issue 6171, page 577, 2014, *Article subject of “Have you seen” commentary in EMBO J vol. 33 no. 4 277-279, 2014, *Article chosen as “Research Highlight” in Nature Rev. Mol. Cell. Biol. 15,150–151, 2014, *Article selected for F1000 “recommended”.
Mohanty, A*., and McBride, H.M. Emerging roles of mitochondria in the evolution, biogenesis and function of peroxisomes. Frontiers in Neuroscience. 2013 Sep 26;4:268. eCollection (Review) CIHR 68833
Lefebvre V, Du Q, Baird S, Ng AC, Nascimento M, Campanella M, McBride HM, Screaton RA. Autophagy. Genome-wide RNAi screen identifies ATPase inhibitory factor 1 (ATPIF1) as essential for PARK2 recruitment and mitophagy. 2013 Autophagy. Nov 1;9(11):1770-9. BRP
Soubannier, V*., Rippstein, P., Kaufman, B.A., Shoubridge, E.A., McBride, HM. Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PLoS One. 2012;7(12):e52830. HSFO 5769
Shutt, TE*, McBride, HM. Staying cool in difficult times: mitochondrial dynamics, quality control and the stress response. Biochim Biophys Acta. 2013 Feb;1833(2):417-24. (Review) CIHR43935
Shutt, T.*, Geoffrion, M., Milne, R., and McBride, HM. The intracellular redox state is a core determinant of mitochondrial fusion. EMBO Rep. 2012 Oct; 3(10); 909-915. CIHR43935
*Article subject of commentary in EMBO Rep. 2012 Oct;13(10):870-1
Soubannier V*, McLelland GL, Zunino R*, Braschi E*, Rippstein P*, Fon EA, McBride HM. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr Biol. 24;22(2):135-41, 2012 HSFO 5769 and BRP
*Article highlighted in Nature Reviews Molecular Cell Biology 13, 63, 2012., *Article selected for Faculty of 1000 “recommended”