Many organelles exist in an equilibrium of fragmentation into smaller units (e.g. during mitosis) and fusion into larger structures. How are size, copy number and shape of an organelle determined and how are the elementary processes of membrane fission and fusion coordinated in order to control these parameters? Yeast vacuoles (lysosomes) can serve as an excellent model to study this question: Vacuoles change copy number and size in the cell cycle and upon shifts of media. Since they are large (up to 5 ?m), facilitating their analysis by fluorescence microscopy, and they are amenable to genetic screening. Moreocontrol these parameters? Yeast vacuoles (lysosomes) can serve as an excellent model to study this question: Vacuoles change copy number and size in the cell cycle and upon shifts of media. Since they aracuoles to study fission on multiple single vacuoles in a defined orientation. These studies will perform important ground work that will lead us towards a comprehensive description of an organelle fission process. They will generate the techniques and materials needed to address, in subsequent studies, how the equilibrium of membrane fission and fusion regulates organelle size and copy number.
Study of organelle biogenesis and homeostasis has revealed numerous connections to heritable diseases, such as mitochondria (myopathies), peroxisomes (Zellweger syndrome), the Golgi apparatus (glycosylation disorders, Batten disease), and lysosomes (lysosomal storage diseases). Among the lysosome-related diseases several cause the Hermansky-Pudlak syndrome - a disease that is linked to problems in lysosome biogenesis and dynamics and that could also be linked to aberrant number, positioning and movements of lysosomes inside the cells. Thus, study of the mechanisms of lysosome division and fragmentation is an important first step in this direction and has potential to uncover molecular mechanisms relevant to human disease.
| Alpadi, Kannan; Kulkarni, Aditya; Comte, Veronique et al. (2012) Sequential analysis of trans-SNARE formation in intracellular membrane fusion. PLoS Biol 10:e1001243 |
