Description
Title: "Mitochondrial metabolic remodeling during Trypanosoma brucei differentiation: when ROS is not SOS
Speaker: 
Alena Zikova, PhD
Group leader,
Institute of Parasitology,
Biology Centre ASCR,
České Budějovice, Czech Republic
Abstract:
The incorporation of mitochondrial reactive oxygen species (mROS) in cellular signaling is an interesting evolutionary outcome, as these potent oxidizers play a role in many pathologies. Available studies on mROS-driven physiological responses are mainly limited to complex cellular systems of metazoans. Here, we utilize the unicellular parasite, Trypanosoma brucei as a simplified but elegant model to define mROS-driven cellular differentiation. This protist undergoes programmed development between different life cycle forms associated with striking changes in the structure and physiology of its single mitochondrion. We mapped this metabolic remodeling in detail and linked elevated ROS levels to the activation of AMP-activated protein kinase (AMPK). Using exogenously expressed mitochondrial catalase, we demonstrated that mROS are essential for AMPK activation and for efficient parasite development. Considering that trypanosomes and metazoans branched early in their evolution, mROS signaling may be one of the first forms of intracellular communication to evolve.
Bio:
I joined the Institute of Parasitology in Ceske Budejovice as a PhD student in 2002, when my supervisor Prof. Julius Lukes introduced RNAi technology to Trypanosoma brucei to study mitochondrial RNA editing. Since then, I have remained loyal to T. brucei and its single mitochondrion, which never ceases to amaze us. After completing my PhD, I spent several years in Ken Stuart's lab at Seattle Biomed mapping the protein-protein interaction network of mitochondrial proteins and diving deeper and deeper into the structural and functional network of this amazing organelle. In my lab, we focus on the mitochondrion of Trypanosoma brucei, which undergoes some of the most extreme metabolic reorganizations known to date during the parasite complex life cycle of the parasite. From amino acid oxidation driving oxidative phosphorylation to aerobic glycolysis, from a fully developed reticular mitochondrion with cristae to a single tubular organelle, from an ATP-producing organelle to an ATP-consuming organelle. Our goal is to understand what signals (extracellular and intracellular) drive the metabolic remodeling of the parasite and the ultrastructural changes of the mitochondria and what are the molecular mechanisms behind them. There are two important outcomes of our work. First, our findings may help in drug development. Second, our findings can shed light on the basic molecular processes that drive metabolic remodeling during cellular differentiation of all eukaryotic cells, including human stem cells, primary immune cells, and cancer cells.
Date: Monday, October 23, 2023
Time: 12-1 pm
Location: Virtually Via Zoom
Questions? Please contact Michael Black if you have questions.