Laboratory of Mitochondrial Biogenesis: Chacinska Laboratory
Description of Current Research
Mitochondria play an important role in metabolism and regulatory processes in the cell. Thus, the formation of mitochondria is essential for cellular function in the entire eukaryotic kingdom, from unicellular organisms to mammals. Mitochondria comprise 1000-1500 cellular proteins, which are synthesized outside of the mitochondria in the cytosol.
The biogenesis of mitochondria relies on the efficient import, sorting, and maturation of proteins governed by conserved protein translocases and other complex machineries. We identified a novel mitochondrial intermembrane space assembly (MIA) pathway that utilizes the transfer of disulfide bonds and is dedicated to the import and biogenesis of intermembrane space proteins that lack a classical mitochondrial leader sequence.
Our research explores novel and exciting links between disulfide bond formation mechanisms and mitochondrial protein homeostasis. We postulate the presence of unique mechanisms involved in protein biogenesis that involve crosstalk between the cytosol and mitochondrial compartments. Our research addresses three major and related issues:
• Redox-related biogenesis events of mitochondrial proteins in yeast and higher eukaryotes.
• The impact of the MIA pathway on mitochondrial and cellular protein homeostasis.
• The biological consequences of oxidative protein biogenesis failure.
Our goal is to better understand the complex and dynamic processes involved in the formation of functional organelles, the maintenance of mitochondrial protein homeostasis, and their failure, which results in pathology.
Our recent publication:
Wrobel L, Topf U, Bragoszewski P , Wiese S, Sztolsztener ME , Oeljeklaus S, Varabyova A, Lirski M, Chroscicki P, Mroczek S, Januszewicz E, Dziembowski A, Koblowska M, Warscheid B, Chacinska A. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. 2015. Nature, 524(7566), 485-8.