Mark RINNERTHALER - Research

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Skin ageing: The skin is our main barrier against the environment and is during our whole life exposed to UV-irradiation, attacks of microbial pathogens and toxic compounds of the environment. Due to its essential role as a barrier the skin is irrespective of such apparent changes as wrinkles an excellent model for aging. This model systems allows to study the aging based on intrinsic factors (genetic factors) as well as extrinsic factors ( the most prominent one being  “photoaging”). The main focus of our research (in tight cooperation with the dermatology at the Paracelsus Medizinische Universität Salzburg) is on the cornified envelope. The cornfied envelope is the outernmost 15 nm thick, very insoluble protein barrier and consists of such proteins as involucrin, filaggrin, “small proline rich proteins”, “late cornifed envelope proteins”, S100 proteins and as its main component loricrin. Our working group found a complete reconstruction of this protein complex during the aging process. At the moment, calcium concentration and other factors are in the main focus of our research as the assumed key players in this CE reorganization. Also age dependant changes in compostion of cytoskeletal proteins are under investigation.

Ageing & Stress Response: Many proteins have more than one function in the cell. Besides their normal role during the cell cycle (the “day job”), many proteins under special conditions have a completely different function (“night job”). Perhaps the most prominent example is the BCL-2 protein family. This family is involved in such processes as the regulation of calcium homeostasis, autophagy, the unfolded protein response and many more. In case of apoptosis these proteins change their function and act as killers (“night job”). In a previous publication we have identified a protein that fulfills a multitude of functions in a healthy cell (interacts with the cytoskeleton,  involved in cell growth regulation, binds Ca2+ or is part of the translation machinery), but is translocating to mitochondria in case of stress or aging. In ongoing research we have identified a domain in this protein that is responsible for this mitochondrial localization that is common to many more proteins. A main goal of this working group is to clarify the role of all these proteins at the mitochondria in case of stress and aging.
One of the most prominent markers of aging is a dramatic increase in reactive oxygen species. The most suspected source of these radicals is the mitochondrial respiratory chain (especially the complex I and III). In general these oxygen radicals are thought to be detrimental to the cell and lead to lipid-peroxidation, DNA and protein damage. In a joint cooperation with the Department of Laboratory Medicine, Paracelsus Medical University Salzburg we want to contradict this general believe that these radicals are only leading to cellular damage and promote aging, but can have a positive effect on the cell on multiple levels.

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