Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons

J Lipid Res. 2019 Jan;60(1):58-70. doi: 10.1194/jlr.M086843. Epub 2018 Nov 15.


Dyslipidemia associated with T2D leads to diabetic neuropathy, a complication characterized by sensory neuronal dysfunction and peripheral nerve damage. Sensory dorsal root ganglion (DRG) neurons are dependent on axonal mitochondrial energy production facilitated by mitochondrial transport mechanisms that distribute mitochondria throughout the axon. Because long-chain saturated FAs (SFAs) damage DRG neurons and medium-chain SFAs are reported to improve neuronal function, we evaluated the impact of SFA chain length on mitochondrial trafficking, mitochondrial function, and apoptosis. DRG neurons were exposed to SFAs with C12:0-C18:0 chain lengths and evaluated for changes in mitochondrial trafficking, mitochondrial polarization, and apoptosis. DRG neurons treated with C16:0 and C18:0 SFAs showed a significant decrease in the percentage of motile mitochondria and velocity of mitochondrial trafficking, whereas C12:0 and C14:0 SFAs had no impact on motility. Treatment with C16:0 and C18:0 SFAs exhibited mitochondrial depolarization correlating with impaired mitochondrial motility; the C12:0- and C14:0-treated neurons retained mitochondrial polarization. The reduction in mitochondrial trafficking and function in C16:0- and C18:0-treated DRG neurons correlated with apoptosis that was blocked in C12:0 and C14:0 SFA treatments. These results suggest that SFA chain length plays an important role in regulating axonal mitochondrial trafficking and function in DRG neurons.

Keywords: apoptosis; diabetes; dyslipidemias; laurate; mitochondrial depolarization; myristate; palmitate; stearate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biological Transport / drug effects
  • Fatty Acids / chemistry*
  • Fatty Acids / pharmacology*
  • Ganglia, Spinal / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Sensory Receptor Cells / cytology*
  • Sensory Receptor Cells / drug effects
  • Structure-Activity Relationship


  • Fatty Acids