SFB 1551 Seminar Series Event – Prof. Dr. Jörg Höhfeld

Talk announcement for Prof. Dr. Jörg Höhfeld.

Maintaining the proteome under mechanical stress – from mechanisms to pathology

By Prof. Dr. Jörg Höhfeld

Universität Bonn · Institut für Zellbiologie

Abstract from Prof. Höhfeld:

Organismal survival depends on the ability to maintain functional protein networks even under conditions that threaten protein integrity. Cells in multicellular organisms are constantly exposed to stress resulting from mechanical forces. In this situation, protein homeostasis relies on a chaperone machinery that is organized by the co-chaperone BAG3. The BAG3-machinery recognizes force-unfolded cytoskeleton proteins and mediates their disposal through chaperone-assisted selective autophagy (CASA). In addition, BAG3 interacts with components of the Hippo and mTOR signalling pathways to stimulate transcription and translation. This is important for compensating degradation during cytoskeleton maintenance. In agreement with its essential role under mechanical stress, BAG3 deficiency causes severe muscle weakness in children and contributes to heart failure, a leading cause of mortality in industrialized nations. Here, we discuss the mode of action of the BAG3-machinery and its force-dependent regulation and pathophysiological relevance.