Protein Homeostasis and the Challenges of Environment, Aging and Disease

The viability of all organisms is critically dependent on a healthy proteome. Proteins drive most, if not all, biological processes including those mediating cell structure, function, and regulation. As physiological conditions fluctuate, the complexity of a proteome is adapted to maintain homeostasis. This balance is challenged by various internal and external events including normal developmental programs as well as environmental or disease conditions. For instance, the emergence of a new tissue type can involve a dynamic rewiring of the protein landscape that is accompanied by increased loads on the protein folding systems in the cytosol and organelles (e.g., endoplasmic reticulum and mitochondria) as well as on the degradation machinery used to clear the obsolete polypeptides. Further contesting the health of a proteome are chronic and acute stresses such as shifts in temperature, free radical, or hydration levels. Fortunately, cells increase the production of protective factors such a molecular chaperones and proteases to counter these insults. A multi-faceted signaling network ensures that proteomic balance is preserved in each cell compartment under all physiological states by utilizing myriad of signaling components as well as gene and translation programs. In conjunction with the molecular chaperones and proteases, these systems constitute the protein homeostasis or proteostasis process. Notably, an organism’s ability to achieve proteostasis dissipates with age correlating with a higher occurrence of aliments including cancer, cardiovascular, metabolic (e.g., type II diabetes), and neurodegenerative diseases.

The 2023 meeting is the eleventh in this successful series and will highlight the most recent advances in the field of protein homeostasis ranging from fundamental mechanisms regulating stress programs and protein quality control to therapeutic strategies countering proteinopathies. Special emphasis will be placed on novel aspects controlling stress-related transcription and translation programs, protein aggregation and phase separation events, polypeptide clearance strategies, and the influence of cytosolic/organelle stress responses to pathology. The collegial and scholarly atmosphere of this conference series encourages vigorous and open discussions of exciting emerging research related to various areas of stress and proteostasis biology. The meeting also provides excellent opportunities for graduate student, postdoctoral fellows, and junior group leaders to present their work either in posters or short talks. We will continue our successful use of “poster preview” talks and a Power Hour focused on women investigators in the field. The formal scientific program, limited attendance, and organized but informal interaction-opportunities help shape this meeting into a preeminent conference promoting a deeper understanding of the versatile roles of stress proteins and proteostasis in human health, aging, and disease.