Sign-up for our newsletter
MAIN
Event Calendar
Awardee Reports
ABOUT DIACOMP
Citing DiaComp
Contact
Committees
Institutions
Awardee Reports
Publications
Bioinformatics
RESOURCES
Protocols & Methods
Reagents & Resources
Mouse Diet
Breeding Schemes
Validation Criteria
IMPC / KOMP Data
Publications
Bioinformatics
CONTACT
PARTICIPANT AREA
Login
▹
Publications
▹
Home
Publication
Diabetes regulates mitochondrial biogenesis and fission in mouse neurons.
Authors
Edwards JL, Quattrini A, Lentz SI, Figueroa-Romero C, Cerri F, Backus C, Hong Y,
Feldman EL
Submitted By
Oliver Smithies on 3/24/2010
Status
Published
Journal
Diabetologia
Year
2010
Date Published
1/1/2010
Volume : Pages
53(1) : 160 - 169
PubMed Reference
19847394
Abstract
AIMS/HYPOTHESIS: Normal mitochondrial activity is a critical component of
neuronal metabolism and function. Disruption of mitochondrial activity by
altered mitochondrial fission and fusion is the root cause of both
neurodegenerative disorders and Charcot-Marie-Tooth type 2A inherited
neuropathy. This study addressed the role of mitochondrial fission in the
pathogenesis of diabetic neuropathy. METHODS: Mitochondrial biogenesis and
fission were assayed in both in vivo and in vitro models of diabetic neuropathy.
Gene, protein, mitochondrial DNA and ultrastructural analyses were used to
assess mitochondrial biogenesis and fission. RESULTS: There was greater
mitochondrial biogenesis in dorsal root ganglion neurons from diabetic compared
with non-diabetic mice. An essential step in mitochondrial biogenesis is
mitochondrial fission, regulated by the mitochondrial fission protein
dynamin-related protein 1 (DRP1). Evaluation of diabetic neurons in vivo
indicated small, fragmented mitochondria, suggesting increased fission. In vitro
studies revealed that short-term hyperglycaemic exposure increased levels of
DRP1 protein. The influence of hyperglycaemia-mediated mitochondrial fission on
cell viability was evaluated by knockdown of Drp1 (also known as Dnm1l).
Knockdown of Drp1 resulted in decreased susceptibility to hyperglycaemic damage.
CONCLUSIONS/INTERPRETATION: We propose that: (1) mitochondria undergo biogenesis
in response to hyperglycaemia, but the increased biogenesis is insufficient to
accommodate the metabolic load; (2) hyperglycaemia causes an excess of
mitochondrial fission, creating small, damaged mitochondria; and (3) reduction
of aberrant mitochondrial fission increases neuronal survival and indicates an
important role for the fission-fusion equilibrium in the pathogenesis of
diabetic neuropathy.
Complications
All Complications
Bioinformatics
Bone
Cardiomyopathy
Cardiovascular
Gastro-Intestinal (GI)
Nephropathy
Neuropathy & Neurocognition
Pediatric Endocrinology
Retinopathy
Uropathy
Wound Healing
Genes
Symbol
Description
Dapk2
death-associated kinase 2
Dnm1
dynamin 1
Dnm1l
dynamin 1-like
Crmp1
collapsin response mediator protein 1
Welcome to the DiaComp Login / Account Request Page.
Email Address:
Password:
Note: Passwords are case-sensitive.
Please save my Email Address on this machine.
Not a member?
If you are a funded DiaComp investigator, a member of an investigator's lab,
or an External Scientific Panel member to the consortium, please
request an account.
Forgot your password?
Enter your Email Address and
click here.
ERROR!
There was a problem with the page:
User Info
User Confirm
Please acknowledge all posters, manuscripts or scientific materials that were generated in part or whole using funds from the Diabetic Complications Consortium(DiaComp) using the following text:
Financial support for this work provided by the NIDDK Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK076169 and DK115255
Citation text and image have been copied to your clipboard. You may now paste them into your document. Thank you!