Project Details
Projekt
Cardiomyocyte Function and Trace Element (TE) Status during Aging: Role of Proteostasis
Applicant
Professor Dr. Tilman Grune
Subject Area
Nutritional Sciences
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 316442145
Iron (Fe) is essential for normal cellular functioning, but in excess, labile reactive Fe enhances oxidative stress, often resulting in a free radical-induced cell death. On the other hand, Fe is crucial for the energy production of cells, especially in cardiomyocytes possessing a high energy demand. In cardiomyocytes, Fe is also required for myoglobin function providing intracellular oxygen transport. Therefore, cardiomyocytes are highly vulnerable to disturbances of Fe metabolism. The functionality of the Fe metabolism is ensured by a number of proteins, which undergo a permanent turnover. Aging is characterized by malfunction of protein turnover, which is mainly due to reduced responses of the ubiquitin-proteasomal system and the autophagy-lysosomal system. This is a dominating process in aging and, therefore, a decline of proteostasis is a hallmark of the aging process. My group has been investigating the degradation of oxidatively modified proteins during aging, including the degradation of proteins of the Fe metabolism, and the regulation of redox-mediated protein degradation for several years. The goal of this project is to systematically investigate, how age-associated changes in proteostasis, in particular proteolytic pathways, effect trace element (TE) status and Fe metabolism-related proteins in cardiomyocytes in relation to cellular function. We will a) establish a correlation between proteolytic pathways and TE-binding and -regulating proteins in aging cardiomyocytes; b) test whether aging per se or hypertrophy as a known phenomenon of aging in cardiomyocytes is the driving factor for age-related TE (Fe) and functional disturbance; and c) test the interaction between various TE occurring during aging or inflammation and Fe metabolism. This will be done in the context with TE profiles of other organs and translated to the human situation.
DFG Programme
Research Units
