Real-time, whole-organism mitochondrial demographics

Mitochondria as any school kid will tell you are the cell's powerhouses, and the ATP-generating biochemistry that drives them is well understood. Only recently however have broader issues of mitochondrial "demographics" been addressed, for example: How many are in a cell? How are they physically distributed? How fast are they reproducing? How interconnected are they? The last question even now would come as a surprise to many biologists, unaware that the ever-familiar multitude of "sausages" represents one end of a continuum at whose other extreme all mitochondria are fused into a single, net-like structure. Being able to adjust mitochondrial connectedness allows cells to switch between a dissociated, readily re-deployable "workforce" and one capable of cell-wide, integrated responses. Mechanistically connectedness is modulated by regulatory proteins that favour either fission or fusion of mitochondrial membranes. The entire field of mitochondrial dynamics is moving ahead apace, providing important insights for general and mammalian biology: recently it was even shown that human optic atrophy can be caused by a mutant mitochondrial fusion protein. Our lab has developed unique and powerful methodologies that are taking the documenting of mitochondrial demographics to a new level. Using high-end microscopy and genetically-introduced fluorescent markers, we can now visualize, in real time, the activities of entire mitochondrial populations throughout whole tissues in a living animal (the fruit-fly, Drosophila melanogaster). We can also track mitochondria in individual cells, both insect and mammalian, at extremely high resolution. For the first time, it is possible to reliably and instantly observe how mitochondrial demographics change under normal, diseased and mutated physiological conditions - a previously undreamed census of the powerhouses' highly fluid citizenry.

• Sriram, V., Krishnan, K.S., Mayor, S. (2003). deep-orange and carnation define distinct stages in late endosomal biogenesis in Drosophila melanogaster. Journal of Cell Biology , 161, 593-607.
• Guha, A., Sriram, V., Krishnan, K.S., and Mayor, S. (2003). shibire mutations reveal distinct Dynamin-independent and dependent endocytic pathways in primary cultures of Drosophila hemocytes. Journal of Cell Science , 116, 3373-3386.