Mitochondria are the cellular powerhouses of the cells, responsible for providing most of the eukaryotic cellular energy. Dynamic changes in cellular energy production are regulated by changes in mitochondrial biomass, by altered activity of metabolic pathways and/or by modulation of mitochondrial metabolic efficiency. The efficiency of mitochondrial ATP production and the the import and export of substrates, such as pyruvate and citrate, depend on the integrity of the proton gradients produced as a function of the mitochondrial electron transport chain. Proton leak currents within the mitochondrial inner membrane, therefore, not only drive the the efficient production of ATP through the F1Fo ATP synthase, they also affect, mitochondrially-mediated processes leading to cellular and synaptic growth and proliferation.
Current Projects
Mitochondria in cancer metabolism
Resistance to cell death and reprogramming of energy metabolism are two prominent features of cancer cells. Mitochondria are known to be intimately linked to both these features and are believed to play a key role in a diversity of processes contributing to the metabolic plasticity and growth of cancer cells. While some cancer types seem to have undergone a metabolic shift to utilize glycolysis for generation of ATP, a number of malignant tumor cells rely mainly on oxidative phosphorylation (OXPHOS) to support their proliferation. Mitochondrial substrates are also utilized in tumour cells for anabolic growth. The process of ATP production through OXPHOS and substrates production for anabolic growth both require an electrochemical gradient across the mitochondrial inner membrane, produced as a result of redox reactions by the electron transport chain. In addition to driving ATP production, the proton gradient is required for passive and active transport of substrates, including pyruvate into the mitochondrial matrix, pumping of cations from matrix and transport of phosphate into the matrix. These processes are impeded by futile leak currents within the inner membrane. We are currently studying the role of ion leak channels in proliferation of glioblastoma multiforme cells.
Mitochondrial energetic efficiency in neuronal plasticity and degeneration
Pharmacological modulation of mitochondrial ion leak currents
Prediction of protein-protein interactions based on whole genome phylogenetic profiles
Mitochondria in cancer metabolism
Resistance to cell death and reprogramming of energy metabolism are two prominent features of cancer cells. Mitochondria are known to be intimately linked to both these features and are believed to play a key role in a diversity of processes contributing to the metabolic plasticity and growth of cancer cells. While some cancer types seem to have undergone a metabolic shift to utilize glycolysis for generation of ATP, a number of malignant tumor cells rely mainly on oxidative phosphorylation (OXPHOS) to support their proliferation. Mitochondrial substrates are also utilized in tumour cells for anabolic growth. The process of ATP production through OXPHOS and substrates production for anabolic growth both require an electrochemical gradient across the mitochondrial inner membrane, produced as a result of redox reactions by the electron transport chain. In addition to driving ATP production, the proton gradient is required for passive and active transport of substrates, including pyruvate into the mitochondrial matrix, pumping of cations from matrix and transport of phosphate into the matrix. These processes are impeded by futile leak currents within the inner membrane. We are currently studying the role of ion leak channels in proliferation of glioblastoma multiforme cells.