Zellen unter Stress : Entspannung mit Hilfe von Proteinen

Wie unsere Zellen mit Stress umgehen, ist eine wichtige Fragestellung auf dem Gebiet der mechanistischen Zellbiologie. Zellen haben Strategien entwickelt, um Stress, der beispielsweise von ungünstigen Wachstumsbedingungen ausgelöst werden kann, wahrzunehmen und sich an diese Gegebenheiten anzupassen. Eine Anpassung ist essentiell, um auch unter schwierigsten Bedingungen das Überleben der Zellen zu sichern. Wenn es den Zellen nicht möglich ist, sich an den Stress anzupassen, können sie auf kontrollierte Weise den eigenen Zelltod auslösen, um das umliegende Gewebe nicht zu schädigen. Um diese komplexen Zusammenhänge im Grundzustand der Zelle und in krankheitsrelevanten Situationen zu verstehen, ist es von großer Wichtigkeit, die zugrundeliegenden molekularen Mechanismen aufzuklären.

How cells respond to stress is an important question in the field of mechanistic cell biology research. Our cells have strategies to sense and adapt to stress, which can be induced by unfavourable growth conditions like high temperature, adverse pH, and starvation but also by work overload of cellular processes. An adaptation to stress is essential to ensure cellular survival even under harsh growth conditions. Alterna-tively, the cell will induce apoptosis, a highly regulated cell death pro-gram, which prevents damage to neighbouring tissue. These stress response mechanisms are intimately connected to cellular protein quality control pathways. Proteins are important cellular bio-molecules exercising specialized, often cell type-specific functions. After being produced, they need to acquire a three dimensional folded structure in order to exercise their functions reliably. Under stress conditions proteins tend to lose their structural integrity. Misfolded proteins act as an important signal for cellular stress, however they are prone to form aggregates and are potentially toxic for the cell. There-fore, quality control mechanisms ensure proper protein folding or lead to the degradation of non-functional proteins. Malfunction of the protein quality control system can eventu-ally lead to pathological conditions such as neurodegenerative diseases. The Golgi apparatus is a cellular organelle important for protein modification, sorting and transport. How the Golgi senses stress, which signals are subsequently induced and how the Golgi maintains protein homeostasis remains largely elusive. Unravelling the molecular mecha-nisms underlying these complex pro-cesses under normal and pathological conditions will enhance our under-standing of fundamental cell biology and provide the basis to develop effective therapies for protein folding diseases.

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