Abstract
Author SummaryAs mitochondria are the main power source for most cells, their correct localization is vital for cellular homeostasis. The morphological and functional complexity of neurons, and the unpredictability of energy demand resulting from sustained impulse activity, means that correct mitochondrial function and location is particularly important for these cells. However, it is unclear how mitochondrial transport responds to the wide range of physiological conduction frequencies experienced by an intact nervous system. Here we image mitochondria moving along mouse saphenous nerve axons in vivo and observe the effects of sustained trains of impulses, evoked either by electrical stimulation of myelinated axons at physiological frequencies (1 and 50 Hz), or chemical stimulation (cutaneous capsaicin) in unmyelinated axons. We find that the number and speed of mitochondria moving towards the peripheral sensory terminals dramatically increases in active axons. The increased numbers of mobile mitochondria seem to originate from “pinched off” segments of stationary mitochondria (mitochondrial fission), and from recruitment of small stationary mitochondria. The transported mitochondria appear to accumulate in sensory nerve terminals in the skin. This study suggests that mitochondrial fission is involved in rapidly supplying mobile mitochondria to aid their re-distribution to regions of increased metabolic demand along axons.
Highlights
Axons can be a metre, or more, in length and mitochondria traffic along them to become correctly distributed to fulfil local metabolic requirements [1]
The morphological and functional complexity of neurons, and the unpredictability of energy demand resulting from sustained impulse activity, means that correct mitochondrial function and location is important for these cells
We image mitochondria moving along mouse saphenous nerve axons in vivo and observe the effects of sustained trains of impulses, evoked either by electrical stimulation of myelinated axons at physiological frequencies (1 and 50 Hz), or chemical stimulation in unmyelinated axons
Summary
Axons can be a metre, or more, in length and mitochondria traffic along them to become correctly distributed to fulfil local metabolic requirements [1]. The study of axonal mitochondrial traffic has largely been limited to in vitro methods, e.g., employing cultured dorsal root ganglia (DRG), organotypic slice cultures [5], or excised myelinated nerves [6]. Organotypic slices and excised nerves may contain myelinated axons, but they have no perfused vasculature providing oxygen and nutrients, lacking physiological regulatory mechanisms crucial for metabolic adaptation in response to increased demand. Excised nerves lack cell bodies and are incipiently undergoing degeneration. To avoid these problems, zebrafish embryos have been used to image mitochondrial trafficking in vivo [7], but it is not known whether developing axons in fish reflect the properties of adult mammalian axons. Axonal mitochondria provide the ATP required to support impulse activity, yet almost no information
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
