Mitochondrial biogenesis and fission in axons in cell culture and animal models
of diabetic neuropathy.
Authors Vincent AM, Edwards JL, McLean LL, Hong Y, Cerri F, Lopez I, Quattrini A,
Feldman EL
Submitted By Eva Feldman on 5/6/2010
Status Published
Journal Acta Neuropathologica
Year 2010
Date Published 10/1/2010
Volume : Pages 120 : 477 - 489
PubMed Reference 20473509
Abstract Mitochondrial-mediated oxidative stress in response to high glucose is proposed
as a primary cause of dorsal root ganglia (DRG) neuron injury in the
pathogenesis of diabetic neuropathy. In the present study, we report a greater
number of mitochondria in both myelinated and unmyelinated dorsal root axons in
a well-established model of murine diabetic neuropathy. No similar changes were
seen in younger diabetic animals without neuropathy or in the ventral motor
roots of any diabetic animals. These findings led us to examine mitochondrial
biogenesis and fission in response to hyperglycemia in the neurites of cultured
DRG neurons. We demonstrate overall mitochondrial biogenesis via increases in
mitochondrial transcription factors and increases in mitochondrial DNA in both
DRG neurons and axons. However, this process occurs over a longer time period
than a rapidly observed increase in the number of mitochondria in DRG neurites
that appears to result, at least in part, from mitochondrial fission. We
conclude that during acute hyperglycemia, mitochondrial fission is a prominent
response, and excessive mitochondrial fission may result in dysregulation of
energy production, activation of caspase 3, and subsequent DRG neuron injury.
During more prolonged hyperglycemia, there is evidence of compensatory
mitochondrial biogenesis in axons. Our data suggest that an imbalance between
mitochondrial biogenesis and fission may play a role in the pathogenesis of
diabetic neuropathy.

Investigators with authorship
Eva FeldmanUniversity of Michigan