Research Group Leader
Laboratory of Metabolic Quality Control in IMol
Dr. Karolina Szczepanowska completed her PhD in 2011 under the supervision of Francoise Foury at the University of Louvain, where she studied the mechanism entangled in mitochondrial genome maintenance. Next, she joined the lab of Aleksandra Trifunovic at the University of Cologne and Cluster of Excellence Cellular Stress Responses in Aging-Associated Disease.
Her postdoctoral research focused on dissecting the secrets of mitochondrial protein homeostasis and quality control in mice, tissue cultures, and worms using advanced proteomic and biochemical approaches. In 2021 she established her research group at the ReMedy/IMol PAS.
"Safeguarding a beautiful beast. The quality control of respiratory Complex I".
The power plant function of mitochondria depends strictly on the elaborate molecular machines embedded inside the mitochondrial membranes, jointly known as the OXPHOS system.
Respiratory Complex I (CI), a beautiful beast of OXPHOS, is the largest respiratory chain complex, and its dysfunction associates with a broad spectrum of diseases. Despite huge advancements in understanding its structure and assembly, the CI quality control and turnover regulation remain enigmatic. The large-scale proteomic studies suggest a highly heterogenous turnover of individual CI subunits. However, underlying mechanisms are mostly elusive.
Our findings indicate that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands a much lower energetic cost than de novo synthesis and reassembly of the entire CI. Furthermore, recent studies suggest that N-module repair can be part of a global quality control system that operates via the concurrent action of proteases and chaperones to keep Complex I in shape.