
Mitochondria are polymorphic, dynamic organelles that play pivotal roles in the life and death processes of eukaryotic cells. They display great heterogeneity in number, shape and location in the cellular milieu for different cell types, appearing as large reticular networks in some cells and as small, punctate, autonomous organelles in others. Non-dividing cells have mitochondria that fuse and divide and, in neurons, they are transported along axons and dendrites. The state of these organelles is determined by an amalgam of processes; mitochondrial biogenesis, fission, fusion, transport and degradation. The mechanisms by which these processes are regulated, and the mechanics of the processes themselves, are poorly understood. However many recent studies have implicated dysregulation of mitochondrial dynamics in neuronal injury. Leber hereditary optic neuropathy (LHON) is an inherited form of blindness that is the result of degeneration of the optic nerve. The disease has been linked to specific mutations in mitochondrial DNA. LHON is the most common form of mitochondrial DNA disorder and there is currently no treatment which halts the disease. Interestingly, in LHON, a mother will pass the mutation to all of her children, but only 50% of male and 10% of female children will suffer vision loss. It is unknown how these mutations cause the nerve death involved in vision loss, and why individuals who possess the mutation do not always develop vision loss. We are exploring the cell biology of LHON through examination of cells from LHON patient tissue biopsies. We hypothesize that cultured human fibroblasts expressing mitochondrial mutations responsible for LHON will demonstrate impaired cellular homeostatic mechanisms and altered mitochondrial dynamics. I will be presenting our latest results examining the role of mitochondria in LHON and the mechanics of changes in mitochondrial dynamics. Findings from these studies may provide insights into the role of mitochondria in other neurodegenerative disorders.

Mitochondria are polymorphic, dynamic organelles that play pivotal roles in the life and death processes of eukaryotic cells. They display great heterogeneity in number, shape and location in the cellular milieu for different cell types, appearing as large reticular networks in some cells and as small, punctate, autonomous organelles in others. Non-dividing cells have mitochondria that fuse and divide and, in neurons, they are transported along axons and dendrites. The state of these organelles is determined by an amalgam of processes; mitochondrial biogenesis, fission, fusion, transport and degradation. The mechanisms by which these processes are regulated, and the mechanics of the processes themselves, are poorly understood. However many recent studies have implicated dysregulation of mitochondrial dynamics in neuronal injury. Leber hereditary optic neuropathy (LHON) is an inherited form of blindness that is the result of degeneration of the optic nerve. The disease has been linked to specific mutations in mitochondrial DNA. LHON is the most common form of mitochondrial DNA disorder and there is currently no treatment which halts the disease. Interestingly, in LHON, a mother will pass the mutation to all of her children, but only 50% of male and 10% of female children will suffer vision loss. It is unknown how these mutations cause the nerve death involved in vision loss, and why individuals who possess the mutation do not always develop vision loss. We are exploring the cell biology of LHON through examination of cells from LHON patient tissue biopsies. We hypothesize that cultured human fibroblasts expressing mitochondrial mutations responsible for LHON will demonstrate impaired cellular homeostatic mechanisms and altered mitochondrial dynamics. I will be presenting our latest results examining the role of mitochondria in LHON and the mechanics of changes in mitochondrial dynamics. Findings from these studies may provide insights into the role of mitochondria in other neurodegenerative disorders.