UC San Diego

Mitochondria, although usually referred to as the powerhouse, is an organelle involved in multiple other biological processes like apoptosis and cell immunity. Mitochondria is also a dynamic organelle that goes through constant and well-regulated fusion and fission events for its proper function. Previous studies about aged cells and neurons affected by neurodegenerative diseases showed a constantly fragmented morphology of mitochondria and mitochondria fragmentation was seen correlated with its dysfunction. However, it is unclear how mitochondria fragmentation causes mitochondria dysfunction. While current model suggests that mitochondria fragmentation results in loss of mitochondrial DNA, which in turn results in mitochondria dysfunction, we believe that the previous studies is not ideal due to the cell lines used all suffered from sustained loss of mitochondrial DNA. Under this condition, it cannot be differentiated whether the dysfunction is due to fragmentation or loss of mitochondrial DNA. Our hypothesis is that mitochondria fragmentation results in heterogeneity in protein expression where each fragment may lack the full set of necessary mitochondrial protein, leading to its dysfunction.In this thesis, I used a fzo1-1 strain of Saccharomyces cerevisiae, in which I could induce mitochondria fragmentation and track its function and mitochondrial DNA immediately after mitochondria fragmentation. The results showed that the mitochondrial membrane potential dropped immediately after mitochondrial fragmentation while the mitochondrial DNA remained at a stable level through out the course of the experiment. These results suggest that initially after mitochondria fragmentation, mitochondrial DNA has minimum effect on loss of mitochondrial membrane potential, which is an important part of mitochondria function, opposite to previous model. I also showed the heterogeneity of MIP1 protein distributed into each mitochondria fragments in a yeast strain with constantly fragmented mitochondria. Both experiments in part support our hypothesis.