Bernard Lemire


Ph.D., University of Alberta                             


Department of Biochemistry
Faculty of Medicine & Dentistry
University of Alberta
445 Medical Sciences Building
Edmonton, Alberta, Canada  T6G 2H7

Tel: 780.492.4853
Lab Tel: 780.492.5546
Fax:  780.492.0886

Energy generation is a vital process for cellular health. Most aerobic organisms use oxidative phosphorylation in mitochondria to meet the majority of their energy needs. Oxidative phosphorylation is performed by the 4 electron transporting proteins of the mitochondrial respiratory chain (MRC) and the ATP synthase. The MRC is the major cellular source of ATP and impaired energy production leads to a bewildering variety of disease conditions, such as myopathies and encephalomyopathies, heart disease, diabetes, and degenerative syndromes such as Parkinson's disease. MRC function is also intimately linked to aging; the MRC is the major site of reactive oxygen species (ROS) production. ROS can damage proteins, DNA, and other macromolecules and it is the accumulation of damage that is associated with the age-related decline in function.
The nematode Caenorhabditis elegans is an excellent model system for investigating the molecular mechanisms of mitochondrial disease and of aging. It is an anatomically simple animal for which a wealth of genetic and developmental information is available. MRC formation requires the expression of 2 genomes, the nuclear and the mitochondrial DNAs (mtDNA). The structure and bioenergetics of the nematode MRC are very similar to the mammalian MRC and the nematode mtDNA is similar in size and gene content to the human mtDNA.
Our goal is to understand the central role of the MRC in cellular health, disease and longevity. We selective isolated and characterize both nDNA and mtDNA mutations. We model human MRC mutations in C. elegans and investigate their mechanisms of pathogenesis. MRC dysfunction results in the impairment of ATP production, the impairment of metabolism and metabolic pathways that control the redox state of the cell, in the production of excess ROS, in the aberrant control of programmed cell death (apoptosis), in premature aging and in aberrant gene expression. Each of these processes contributes to the overall disease pathology and progression. We have employed pharmacological agents and gene therapy to mitigate or correct the effects of MRC dysfunction. Mitochondrial activity is intimately linked to lifespan determination. Signaling along several pathways can extend nematode lifespan and we have shown that these pathways converge on mitochondrial function. We are actively pursuing how the regulation of mitochondrial energy generation is associated with extended lifespan.



Szeto SS, Reinke SN, Oyedotun KS, Sykes BD and Lemire BD (2012) Expression of Saccharomyces cerevisiae Sdh3p and Sdh4p paralogs results in catalytically active succinate dehydrogenase isoenzymes. J Biol. Chem, (available online May 9, 2012)
Szeto SS, Reinke SN, Lemire BD (2011) 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems. J Biomol NMR, 49:245-254.
Reinke SN, Hu X, Sykes BD, Lemire BD (2010) Caenorhabditis elegans diet significantly affects metabolic profile, mitochondrial DNA levels, lifespan and brood size. Mol Genet Metab, 100:274-282.
Lemire BD, Behrendt M, DeCorby A and Gášková D. (2009) C. elegans longevity pathways converge to decrease mitochondrial membrane potential. Mech Ageing Dev. 130:461-465. 
Huang J and Lemire BD. (2009) Mutations in the C. elegans succinate dehydrogenase iron-sulfur subunit promote superoxide generation and premature aging. J Mol Biol, 387:559-569. 
Tsang WY and Lemire, BD. (2003) The role of mitochondria in the life of the nematode, Caenorhabditis elegans.  Biochim. Biophys. Acta 1638:91– 105.