Forschung/Research

Mitochondrial Biology 

Mitochondrial dynamics and quality control of mitochondria
Our group aims to elucidate the link of mitochondrial dynamics and degradation of damaged mitochondria by mitophagy and to decipher the mechanisms determining mitochondrial ultrastructure. The mitochondrial network in cells is highly dynamic and mitochondrial fusion and fission as well as redistribution and degradation of mitochondria do occur constantly. Fusion and fission are predicted to be essential for quality control of mitochondria as in many diseases the balance between fusion and fission is affected. Furthermore, dysfunctional mitochondria are unable to fuse to the intact mitochondrial network and it was proposed that this is a prerequisite for distinguishing functional from dysfunctional mitochondria. We study the process of selective degradation of mitochondria as dysfunctional mitochondria can be degraded via mitophagy and an impaired degradation and the consequential accumulation of dysfunctional mitochondria seem to play an important role in the aging process and the pathogenesis of numerous human disorders. Another focus of our research is to understand the molecular mechanisms that shape the inner mitochondrial membrane, particularly, cristae and crista junctions and their importance in cellular viability.


Fig. 01: Mitochondria visualized by fluorescence microscopy. Left, two baker's yeast cells expressing mitochondrial green fluorescent protein (mt-GFP). Right, Mammalian cells (HeLa cell line) stained for mitochondria (red) and the nucleus (blue).


Fig. 02: Cristae morphology in a yeast strain lacking Fcj1. A surface rendered view of an EM tomogram of a mitochondrium is shown (from Rabl et al. 2009). The inner membrane (yellow) shows cristae membranes arranged in parallel concentric stacks lacking crista junctions.

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AG Reichert

 

 

Biochemistry of Oxidative Stress in health and disease

Another main area of research of the institute is the biochemistry of oxidative stress in context of physiological and pathophysiological processes.  In general, the term „Oxidative Stress“ describes an imbalance between prooxidants (reactive oxygen species, ROS)  and antioxidants towards a higher level of ROS, a concept first described by H. Sies and others. For example, aerobic processes of the metabolism, photobiological effects, the body's own (immune) defense, and exogenous noxious substances may generate reactive oxygen species. If ROS are not detoxified by endogenous or exogenous antioxidants, ROS may damage macromolecules such as nucleic acids, proteins, and lipids, affecting the redox-status of the cell and the underlying (redox)signaling and finally leading to a pathobiochemical fate of the appropriate cells. These cellular changes, if not counteracted, result in a pathobiochemical/-physiological state of the affected tissue and organ, the source of diseases such as cancer and cardiovascular, neurodegenerative, and liver diseases. Furthermore, ROS initiate the expression of genes which are involved in processes of (photo)aging.

To elucidate and understand the molecular mechanisms underlying a biochemical or pathobiochemical state, cell biological, biochemical, and molecular biological methods are used. Intervention studies on cells, in-vitro 3D-models, animals, and people are performed and deal with both the modulation of endogenous enzymatic and non-enzymatic antioxidants  and the use of effective antioxidant substances such as vitamin C and E, carotenoids, polyphenols, selenium compounds, and (redox-active) nanoparticles to prevent or to counteract the pathological molecular processes.

The antioxidant ingredients of plants ingested with the food may be a strategy in prevention of some diseases. In that context, epidemiological studies have shown, that an increased consumption of food enriched with antioxidants reduce the risc of some types of cancer and cardiovascular diseases. Furthermore, it was shown at the institute, that redox-active nanoparticles exert a bifunctional role, being an antioxidant in healthy cells and being a prooxidant in tumor cells.  

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AG Brenneisen

AG Stahl

 
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  • Zuletzt aktualisiert am 17.09.2015
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