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Université de Fribourg

Mitophagy as a stress response in mammalian cells and in respiring S. cerevisiae

Abeliovich, Hagai ; Dengjel, Jörn

In: Biochemical Society Transactions, 2016, vol. 44, no. 2, p. 541–545

The degradation of malfunctioning or superfluous mitochondria in the lysosome/vacuole is an important housekeeping function in respiring eukaryotic cells. This clearance is thought to occur by a specific form of autophagic degradation called mitophagy, and plays a role in physiological homoeostasis as well as in the progression of late-onset diseases. Although the mechanism of bulk...

Université de Fribourg

Phosphoproteomic profiling reveals a defined genetic program for osteoblastic lineage commitment of human bone marrow–derived stromal stem cells

Barrio-Hernandez, Inigo ; Jafari, Abbas ; Rigbolt, Kristoffer T.G. ; Hallenborg, Philip ; Sanchez-Quiles, Virginia ; Skovrind, Ida ; Akimov, Vyacheslav ; Kratchmarova, Irina ; Dengjel, Jörn ; Kassem, Moustapha ; Blagoev, Blagoy

In: Genome Research, 2020, vol. 30, no. 1, p. 127-137

Bone marrow–derived mesenchymal stem cells (MSCs) differentiate into osteoblasts upon stimulation by signals present in their niche. Because the global signaling cascades involved in the early phases of MSCs osteoblast (OB) differentiation are not well-defined, we used quantitative mass spectrometry to delineate changes in human MSCs proteome and phosphoproteome during the first 24 h of...

Université de Fribourg

Influenza A virus induces autophagosomal targeting of ribosomal proteins

Becker, Andrea C. ; Gannagé, Monique ; Giese, Sebastian ; Hu, Zehan ; Abou-Eid, Shadi ; Roubaty, Carole ; Paul, Petra ; Bühler, Lea ; Gretzmeier, Christine ; Dumit, Veronica I. ; Kaeser-Pebernard, Stéphanie ; Schwemmle, Martin ; Münz, Christian ; Dengjel, Jörn

In: Molecular & Cellular Proteomics, 2018, vol. 17, no. 10, p. 1909–1921

Seasonal epidemics of influenza A virus are a major cause of severe illness and are of high socio-economic relevance. For the design of effective antiviral therapies, a detailed knowledge of pathways perturbed by virus infection is critical. We performed comprehensive expression and organellar proteomics experiments to study the cellular consequences of influenza A virus infection using three...

Université de Fribourg

Proteomic profiling of fibroblasts isolated from chronic wounds identifies disease-relevant signaling pathways

Berberich, Bettina ; Thriene, Kerstin ; Gretzmeier, Christine ; Kühl, Tobias ; Bayer, Hans ; Athanasiou, Ioannis ; Rafei-Shamsabadi, David Ali ; Bruckner-Tuderman, Leena ; Nyström, Alexander ; Kiritsi, Dimitra ; Dengjel, Jörn

In: Journal of Investigative Dermatology, 2020, vol. 140, no. 11, p. 2280-2290.e4

Chronic skin wounds accompany many prevalent age-related diseases and are a major cause of morbidity and mortality. Both keratinocytes and fibroblasts contribute to the pathomechanisms in chronic skin wounds. Dysregulated pathways in the epidermis have been extensively studied, but little is known of the influence of dermal fibroblasts on chronic wounding. We isolated fibroblasts from chronic...

Université de Fribourg

Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock

Brenna, Andrea ; Olejniczak, Iwona ; Chavan, Rohit ; Ripperger, Jürgen A. ; Langmesser, Sonja ; Cameroni, Elisabetta ; Hu, Zehan ; De Virgilio, Claudio ; Dengjel, Jörn ; Albrecht, Urs

In: eLife, 2019, vol. 8, p. e50925

Circadian oscillations emerge from transcriptional and post-translational feedback loops. An important step in generating rhythmicity is the translocation of clock components into the nucleus, which is regulated in many cases by kinases. In mammals, the kinase promoting the nuclear import of the key clock component Period 2 (PER2) is unknown. Here, we show that the cyclin-dependent kinase 5...

Université de Fribourg

Beyond global charge: role of amine bulkiness and protein fingerprint on nanoparticle–cell interaction

Burnand, David ; Milosevic, Ana ; Balog, Sandor ; Spuch-Calvar, Miguel ; Rothen-Rutishauser, Barbara ; Dengjel, Jörn ; Kinnear, Calum ; Moore, Thomas L. ; Petri-Fink, Alke

In: Small, 2018, vol. 14, no. 46, p. 1802088

Amino groups presented on the surface of nanoparticles are well‐known to be a predominant factor in the formation of the protein corona and subsequent cellular uptake. However, the molecular mechanism underpinning this relationship is poorly defined. This study investigates how amine type and density affect the protein corona and cellular association of gold nanoparticles with cells in...

Université de Fribourg

The flavonoid 4,4′-dimethoxychalcone promotes autophagy-dependent longevity across species

Carmona-Gutierrez, Didac ; Zimmermann, Andreas ; Kainz, Katharina ; Pietrocola, Federico ; Chen, Guo ; Maglioni, Silvia ; Schiavi, Alfonso ; Nah, Jihoon ; Mertel, Sara ; Beuschel, Christine B. ; Castoldi, Francesca ; Sica, Valentina ; Trausinger, Gert ; Raml, Reingard ; Sommer, Cornelia ; Schroeder, Sabrina ; Hofer, Sebastian J. ; Bauer, Maria A. ; Pendl, Tobias ; Tadic, Jelena ; Dammbrueck, Christopher ; Hu, Zehan ; Ruckenstuhl, Christoph ; Eisenberg, Tobias ; Durand, Sylvere ; Bossut, Noélie ; Aprahamian, Fanny ; Abdellatif, Mahmoud ; Sedej, Simon ; Enot, David P. ; Wolinski, Heimo ; Dengjel, Jörn ; Kepp, Oliver ; Magnes, Christoph ; Sinner, Frank ; Pieber, Thomas R. ; Sadoshima, Junichi ; Ventura, Natascia ; Sigrist, Stephan J. ; Kroemer, Guido ; Madeo, Frank

In: Nature Communications, 2019, vol. 10, no. 1, p. 651

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′- dimethoxychalcone (DMC) as a natural compound with anti-ageing...

Université de Fribourg

Skin proteomics – analysis of the extracellular matrix in health and disease

Dengjel, Jörn ; Bruckner-Tuderman, Leena ; Nyström, Alexander

In: Expert Review of Proteomics, 2020, vol. 17, no. 5, p. 377–391

Introduction The skin protects the human body from external insults and regulates water and temperature homeostasis. A highly developed extracellular matrix (ECM) supports the skin and instructs its cell functions. Reduced functionality of the ECM is often associated with skin diseases that cause physical impairment and also have implications on social interactions and quality of life of...

Université de Fribourg

Roles of mitophagy in cellular physiology and development

Dengjel, Jörn ; Abeliovich, Hagai

In: Cell and Tissue Research, 2017, vol. 367, no. 1, p. 95–109

The autophagic degradation of mitochondria, or mitophagy, has been shown to occur in eukaryotic cells under various physiological conditions. Broadly, these fall into two categories: quality-control related mitophagy and developmentally induced mitophagy. Quality-control related mitophagy, which is the lysosomal/vacuolar degradation of malfunctioning or superfluous mitochondria, is an...

Université de Fribourg

Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition

Diedrich, Britta ; Rigbolt, Kristoffer TG ; Röring, Michael ; Herr, Ricarda ; Kaeser‐Pebernard, Stephanie ; Gretzmeier, Christine ; Murphy, Robert F ; Brummer, Tilman ; Dengjel, Jörn

In: The EMBO Journal, 2017, vol. 36, no. 5, p. 646–663

As a central element within the RAS/ERK pathway, the serine/threonine kinase BRAF plays a key role in development and homeostasis and represents the most frequently mutated kinase in tumors. Consequently, it has emerged as an important therapeutic target in various malignancies. Nevertheless, the BRAF activation cycle still raises many mechanistic questions as illustrated by the paradoxical...