Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

SIMPLE SUMMARY: Mitochondria are organelles within our cells that are best known for their role in energy production. They are also able to fuse, divide, and move within the cell (referred to as mitochondrial dynamics). This is especially important in neurons, where cells can be very long as they travel in peripheral nerves to send signals to muscles or detect sensory stimuli. Problems with mitochondrial dynamics can result in a spectrum of human diseases, ranging from milder disease in late adulthood through to severe, lethal, early onset diseases. In this review, we discuss the important genes involved in mitochondrial dynamics that have also been connected with genetic neuropathies. We explain how these gene products interact to maintain normal mitochondrial functions and describe some common themes, such as mitochondrial quality control. ABSTRACT: Mitochondria are dynamic organelles capable of fusing, dividing, and moving about the cell. These properties are especially important in neurons, which in addition to high energy demand, have unique morphological properties with long axons. Notably, mitochondrial dysfunction causes a variety of neurological disorders including peripheral neuropathy, which is linked to impaired mitochondrial dynamics. Nonetheless, exactly why peripheral neurons are especially sensitive to impaired mitochondrial dynamics remains somewhat enigmatic. Although the prevailing view is that longer peripheral nerves are more sensitive to the loss of mitochondrial motility, this explanation is insufficient. Here, we review pathogenic variants in proteins mediating mitochondrial fusion, fission and transport that cause peripheral neuropathy. In addition to highlighting other dynamic processes that are impacted in peripheral neuropathies, we focus on impaired mitochondrial quality control as a potential unifying theme for why mitochondrial dysfunction and impairments in mitochondrial dynamics in particular cause peripheral neuropathy.