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Faculty of MedicineCenter for Biochemistry

About the Lemberg Lab

Research in the Lemberg Laboratory focuses on the study of protein homeostasis mechanisms that act in the plane of cellular membranes. Our team is particularly interested in the physiological role and regulation of intramembrane proteases and transmembrane dislocases, unravelling the mechanisms to extract proteins from the membrane and coordinate their degradation by the cytosolic ubiquitin proteasome system. Our research direction will reveal a comprehensive understanding of these protein homeostasis mechanisms and shed light on potential targets for therapeutic intervention strategies to overcome the effects of protein homeostasis malfunction in disorders ranging from Parkinson’s disease to neuropathies.

 

Deregulated intramembrane proteolysis induces change in the morphology of the endplasmic reticulum.

Research Focus

Biochemist and cell biologist Marius Lemberg investigates intramembrane proteolysis and protein homeostasis mechanisms in health and disease.

 

Selected publications

Original Papers

  1. Knopf JD, Steigleder SS, Korn K, Kühnle N, Badenes M, Tauber M, Theobald SJ, Rybniker J, Adrain A, Lemberg MK. RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling. Nat. Commun. 15: 1528, 2024.
  2. Zanotti A, Coelho JPL, Kaylani D, Singh G, Tauber M, Hitzenberger M, Avci D, Zacharias M, Russell RB, Lemberg MK*, Feige MJ*. The Human Signal Peptidase Complex Acts as a Quality Control Enzyme for Membrane Proteins. Science 378: 996-1000, 2022
  3. Engberg O, Ulbricht D, Döbel V, Siebert V, Frie C, Penk A, Lemberg MK*, Huster D*. Rhomboid-catalyzed intramembrane proteolysis requires hydrophobic matching with the surrounding lipid bilayer. Sci Adv. 8: eabq8303, 2022.
  4. Bock J, Kühnle N, Knopf JD, Landscheidt N, Lee JG, Ye Y, Lemberg MK. Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation. Cell Rep. 40: 111175, 2022.
  5. Siebert V, Silber M, Heuten E, Muhle-Goll C, Lemberg MK. Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state. J Biol Chem. 298: 102321, 2022.
  6. Dederer V, Khmelinskii A, Huhn A, Okreglak V, Knop M, Lemberg MK. Cooperation of mitochondrial and ER factors in quality control of tail-anchored proteins. eLife 8: e45506, 2019.
  7. Meissner C, Lorenz H, Hehn B, Lemberg MK. Intramembrane protease PARL defines a negative regulator of PINK1- and PARK2/Parkin-dependent mitophagy. Autophagy. 11: 1484-1498, 2015.
  8. Avci D, Fuchs S, Schrul B, Fukumori A, Breker M, Frumkin I, Chen C, Biniossek ML, Kremmer E, Schilling O, Steiner H, Schuldiner M*, Lemberg MK*. The yeast ER-intramembrane protease Ypf1 refines nutrient sensing by regulating transporter abundance. Mol. Cell. 56: 630-640, 2014.
  9. Chen C, Malchus NS, Hehn B, Stelzer W, Avci D, Langosch D, Lemberg MK. Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u. EMBO J. 33: 2492-2506, 2014.
  10. Fleig L, Bergbold N, Sahasrabudhe P, Geiger B, Kaltak L, Lemberg MK. Ubiquitin-Dependent Intramembrane Rhomboid Protease Promotes ERAD of Membrane Proteins. Mol Cell. 47: 558-569, 2012.
Reviews

  1. Dederer V, Lemberg MK. Transmembrane dislocases: a second chance for protein targeting. Trends Cell Biol. 2021.
  2. Lemberg MK, Strisovsky K. Maintenance of organellar protein homeostasis by ER-associated degradation and related mechanisms. Mol. Cell 81: 2507-2519, 2021.
  3. Kuehnle N, Dederer V, Lemberg MK. Intramembrane proteolysis at a glance: from signalling to protein degradation. J. Cell Sci. 132: jcs.217745, 2019.

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