Abstract
Simple SummaryMitochondria 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. 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.
Highlights
The term mitochondrial dynamics typically refers to the reciprocal processes of mitochondrial fusion and fission, which determine the morphology of the mitochondrial network
While impaired mitochondrial transport is typically thought to explain the peripheral neuropathy phenotype associated with pathogenic variants in genes regulating mitochondrial dynamics, there is likely more to the story
Given that transport problems alone cannot explain why impaired mitochondrial dynamics cause peripheral neuropathy, we propose that mitochondrial quality control is an underappreciated aspect of mitochondrial dynamics that is relevant to peripheral neuropathy
Summary
The term mitochondrial dynamics can be expanded to include processes such as the transport of mitochondria [1], mitochondrial interactions with other organelles [2], as well as the biogenesis of new mitochondria, and the turnover of old or damaged mitochondria via mitochondrial autophagy (mitophagy) [3] or small mitochondrial derived vesicles [4]. Fission is required to generate fragments that are small enough to be degraded by mitophagy, or to move about the cell prior to fusing with other mitochondria These dynamic processes allow mitochondria to adapt to physiological cues and are critical in maintaining cellular energetics, Ca2+ signaling, lipid biogenesis, mitochondrial quality control, and cell survival
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
