Principal Investigators
Thomas Langer

Fax  +49 221 478 84261

CECAD Cologne
CECAD Forschungszentrum
Joseph-Stelzmann-Str. 26
D 50931 Köln
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Prof. Thomas Langer

A dysfunction of mitochondria, the powerhouses of the cell, has severe cellular consequences and is linked to aging and neurodegeneration. We are interested in cellular surveillance strategies that have evolved to limit mitochondrial damage and ensure cellular integrity. Protein quality control, executed by various intramitochondrial proteases, and the dynamic fusion and fission of mitochondrial membranes are emerging as key processes in the molecular network governing aging and life-span. Impairment of these systems is associated with various neurodegenerative disorders that form the focus of our research. Studies on AAA proteases, energy-dependent quality control enzymes in the inner membrane of mitochondria, and associated prohibitin scaffold complexes have unraveled important regulatory functions for biogenesis and fusion of mitochondrial membranes and highlight the importance of inner membrane integrity for mitochondrial activities and neuronal survival. The stress-induced processing of the dynamin-like GTPase OPA1 by the novel peptidase OMA1 has been identified as a potential sensing mechanism for mitochondrial dysfunction, offering novel approaches for genetic and biochemical interventions.

Figures
Figure 1: 3D-reconstruction of Neurospora crassa mitochondria by electron microscopy.
Figure 1
Figure 2+3: Cryo-electron-microscopic reconstructions of hexameric m-AAA proteases (top view).
Figure 2
Figure 4: Mitochondrial fragmentation and perinuclear clustering in PHB2-deficient murine hippocampal neurons. Mitochondria were visualized expressing mitochondrially targeted EGFP (green). The nucleus was stained with DAPI (blue) and neuronal βIII-tubulin by immunofluorescence (red).
Figure 3
Figure 5: Electron microscopy of murine hippocampal mitochondria.
Figure 4
Figure 6: Structural model of the AAA ATPase ring of the yeast m-AAA protease based on the crystal structure of bacterial FtsH. A substrate binding region is highlighted in red.
Figure 5
Figure 6

Figure 1: 3D-reconstruction of Neurospora crassa mitochondria by electron microscopy.

Figure 2+3: Cryo-electron-microscopic reconstructions of hexameric m-AAA proteases (top view).

Figure 4: Mitochondrial fragmentation and perinuclear clustering in PHB2-deficient murine hippocampal neurons. Mitochondria were visualized expressing mitochondrially targeted EGFP (green). The nucleus was stained with DAPI (blue) and neuronal βIII-tubulin by immunofluorescence (red).

Figure 5: Electron microscopy of murine hippocampal mitochondria.

Figure 6: Structural model of the AAA ATPase ring of the yeast m-AAA protease based on the crystal structure of bacterial FtsH. A substrate binding region is highlighted in red.