Function and regulation of the mitochondrial membrane fusion machinery

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Mitochondria are amazingly dynamic organelles of eukaryotic cells. In many cell types, they continuously move along cytoskeletal tracks and frequently fuse and divide. Mitochondrial dynamics is critical for cell life or death, because it plays a key role in the initiation of the programmed cell death pathway (apoptosis), and mitochondrial fusion constitutes a defence mechanism against cellular aging. The molecular machinery mediating mitochondrial fusion and fission has been highly conserved during evolution. Thus, it can be conveniently studied in simple model organisms, such as yeasts and filamentous fungi. During the past few years, three components of the core machinery mediating mitochondrial fusion and two regulatory factors have been identified in yeast. However, the molecular mechanisms of mitochondrial membrane fusion are only poorly understood, and given the complexity of this process additional yet unknown factors likely exist. The proposed project is aimed at the functional characterization of the known proteins of the mitochondrial fusion machinery of yeast and Neurospora crassa employing established and novel in vivo and in vitro assays. Furthermore, the identification and functional characterization of novel components in yeast will help to understand the complex process of mitochondrial double membrane fusion at a molecular level.