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

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 mechanism...

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Main Authors: Amy E. Rumora, Giovanni LoGrasso, Julia A. Haidar, Justin J. Dolkowski, Stephen I. Lentz, Eva L. Feldman
Format: Article
Language:English
Published: Elsevier 2019-01-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520326651
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author Amy E. Rumora
Giovanni LoGrasso
Julia A. Haidar
Justin J. Dolkowski
Stephen I. Lentz
Eva L. Feldman
author_facet Amy E. Rumora
Giovanni LoGrasso
Julia A. Haidar
Justin J. Dolkowski
Stephen I. Lentz
Eva L. Feldman
author_sort Amy E. Rumora
collection DOAJ
description 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.
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spelling doaj.art-331716c6c3ab44e6a916cf6594627d9d2022-12-21T22:09:10ZengElsevierJournal of Lipid Research0022-22752019-01-016015870Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neuronsAmy E. Rumora0Giovanni LoGrasso1Julia A. Haidar2Justin J. Dolkowski3Stephen I. Lentz4Eva L. Feldman5Departments of Neurology University of Michigan, Ann Arbor, MI 48109Departments of Neurology University of Michigan, Ann Arbor, MI 48109Departments of Neurology University of Michigan, Ann Arbor, MI 48109Departments of Internal Medicine, University of Michigan, Ann Arbor, MI 48109Departments of Internal Medicine, University of Michigan, Ann Arbor, MI 48109To whom correspondence should be addressed; Departments of Neurology University of Michigan, Ann Arbor, MI 48109; To whom correspondence should be addressedDyslipidemia 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.http://www.sciencedirect.com/science/article/pii/S0022227520326651diabetesdyslipidemiasapoptosispalmitatestearatelaurate
spellingShingle Amy E. Rumora
Giovanni LoGrasso
Julia A. Haidar
Justin J. Dolkowski
Stephen I. Lentz
Eva L. Feldman
Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
Journal of Lipid Research
diabetes
dyslipidemias
apoptosis
palmitate
stearate
laurate
title Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
title_full Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
title_fullStr Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
title_full_unstemmed Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
title_short Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
title_sort chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons
topic diabetes
dyslipidemias
apoptosis
palmitate
stearate
laurate
url http://www.sciencedirect.com/science/article/pii/S0022227520326651
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AT juliaahaidar chainlengthofsaturatedfattyacidsregulatesmitochondrialtraffickingandfunctioninsensoryneurons
AT justinjdolkowski chainlengthofsaturatedfattyacidsregulatesmitochondrialtraffickingandfunctioninsensoryneurons
AT stephenilentz chainlengthofsaturatedfattyacidsregulatesmitochondrialtraffickingandfunctioninsensoryneurons
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