IOCB Prague

Kvido Stříšovský Group

Intramembrane Proteolysis and Biological Regulation
Research Group
Senior
BIO cluster

About our group

The research in Strisovsky lab is focused on biological membranes and enzymatic catalysis occurring in their context. We are studying the ubiquitous intramembrane proteases of the rhomboid family and the mechanistic aspects of their functions relevant for biological signaling, membrane protein biogenesis and homeostasis. In our work we integrate the tools of membrane biochemistry, enzymology and structural biology to understand how rhomboid proteases recognise and select substrates, and employ methods of quantitative proteomics, cell biology and genetics to uncover molecular basis of rhomboid functions in organisms. We are an international group and we are always eager to consider motivated students and postdocs who would like to join us. If interested, contact Kvido Strisovsky.

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Publications

All publications
Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy
Chemical Blockage of the Mitochondrial Rhomboid Protease PARL by Novel Ketoamide Inhibitors Reveals Its Role in PINK1/Parkin-Dependent Mitophagy
Journal of Medicinal Chemistry 66 (1): 251–265 (2023)
The mitochondrial rhomboid protease PARL regulates mitophagy by balancing intramembrane proteolysis of PINK1 and PGAM5. It has been implicated in the pathogenesis of Parkinson’s disease, but its investigation as a possible therapeutic target is challenging in this context because genetic deficiency of PARL may result in compensatory mechanisms. To address this problem, we undertook a hitherto unavailable chemical biology strategy. We developed potent PARL-targeting ketoamide inhibitors and investigated the effects of acute PARL suppression on the processing status of PINK1 intermediates and on Parkin activation. This approach revealed that PARL inhibition leads to a robust activation of the PINK1/Parkin pathway without major secondary effects on mitochondrial properties, which demonstrates that the pharmacological blockage of PARL to boost PINK1/Parkin-dependent mitophagy is a feasible approach to examine novel therapeutic strategies for Parkinson’s disease. More generally, this study…
EMC is required for biogenesis of Xport-A, an essential chaperone of Rhodopsin-1 and the TRP channel
Embo Reports 23 (1): e53210 (2022)
Maintenance of organellar protein homeostasis by ER-associated degradation and related mechanisms
Molecular Cell 81 (12): 2507-2519 (2021)
Rhomboid intramembrane protease YqgP licenses bacterial membrane protein quality control as adaptor of FtsH AAA protease
EMBO Journal 39 (10): e102935 (2020)
General and Modular Strategy for Designing Potent, Selective, and Pharmacologically Compliant Inhibitors of Rhomboid Proteases
Cell Chemical Biology 24 (12): 1523-1536 (2017)