Khan, NA;
Auranen, M;
Paetau, I;
Pirinen, E;
Euro, L;
Forsström, S;
Pasila, L;
Velagapudi, V;
Carroll, CJ;
Auwerx, J;
et al.
Khan, NA; Auranen, M; Paetau, I; Pirinen, E; Euro, L; Forsström, S; Pasila, L; Velagapudi, V; Carroll, CJ; Auwerx, J; Suomalainen, A
(2014)
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3.
EMBO Mol Med, 6 (6).
pp. 721-731.
ISSN 1757-4684
https://doi.org/10.1002/emmm.201403943
SGUL Authors: Carroll, Christopher John
Abstract
Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD(+) precursor, was previously shown to boost NAD(+) levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD(+) levels are a promising treatment strategy for mitochondrial myopathy.
Item Type: |
Article
|
Additional Information: |
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2014 The Authors. Published under the terms of the CC BY license |
Keywords: |
NAD+, mitochondrial myopathy, nicotinamide riboside, treatment, unfolded protein response, Adipose Tissue, Brown, Animals, Energy Metabolism, Forkhead Box Protein O1, Forkhead Transcription Factors, Lipid Metabolism, Liver, Male, Mice, Mice, Inbred C57BL, Mitochondria, Mitochondrial Myopathies, Muscle, Skeletal, NAD, Niacinamide, Sirtuin 1, Unfolded Protein Response, Vitamin B Complex, 06 Biological Sciences, 11 Medical And Health Sciences |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS) |
Journal or Publication Title: |
EMBO Mol Med |
ISSN: |
1757-4684 |
Language: |
eng |
Dates: |
Date | Event |
---|
June 2014 | Published | 6 April 2014 | Published Online | 17 March 2014 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
R01 AG043930 | NIA NIH HHS | UNSPECIFIED | R01 HL106511 | NHLBI NIH HHS | UNSPECIFIED | R01AG043930 | NIA NIH HHS | UNSPECIFIED | R01HL106511-01A | NHLBI NIH HHS | UNSPECIFIED |
|
PubMed ID: |
24711540 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/109276 |
Publisher's version: |
https://doi.org/10.1002/emmm.201403943 |
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