Disentangling the effect of dietary restriction on mitochondrial function using recombinant inbred mice

Mulvey, L., Sands, W. A., Salin, K., Carr, A. E. and Selman, C. (2017) Disentangling the effect of dietary restriction on mitochondrial function using recombinant inbred mice. Molecular and Cellular Endocrinology, 455, pp. 41-53. (doi:10.1016/j.mce.2016.09.001) (PMID:27597651)

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Abstract

Dietary restriction (DR) extends lifespan and healthspan in many species, but precisely how it elicits its beneficial effects is unclear. We investigated the impact of DR on mitochondrial function within liver and skeletal muscle of female ILSXISS mice that exhibit strain-specific variation in lifespan under 40% DR. Strains TejJ89 (lifespan increased under DR), TejJ48 (lifespan unaffected by DR) and TejJ114 (lifespan decreased under DR) were studied following 10 months of 40% DR (13 months of age). Oxygen consumption rates (OCR) within isolated liver mitochondria were unaffected by DR in TejJ89 and TejJ48, but decreased by DR in TejJ114. DR had no effect on hepatic protein levels of PGC-1a, TFAM, and OXPHOS complexes IV. Mitonuclear protein imbalance (nDNA:mtDNA ratio) was unaffected by DR, but HSP90 protein levels were reduced in TejJ114 under DR. Surprisingly hepatic mitochondrial hydrogen peroxide (H2O2) production was elevated by DR in TejJ89, with total superoxide dismutase activity and protein carbonyls increased by DR in both TejJ89 and TejJ114. In skeletal muscle, DR had no effect on mitochondrial OCR, OXPHOS complexes or mitonuclear protein imbalance, but H2O2 production was decreased in TejJ114 and nuclear PGC-1a increased in TejJ89 under DR. Our findings indicate that hepatic mitochondrial dysfunction associated with reduced lifespan of TejJ114 mice under 40% DR, but similar dysfunction was not apparent in skeletal muscle mitochondria. We highlight tissue-specific differences in the mitochondrial response in ILSXISS mice to DR, and underline the importance and challenges of exploiting genetic heterogeneity to help understand mechanisms of ageing.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mulvey, Ms Lorna and Selman, Professor Colin and Sands, Dr William and Salin, Dr Karine
Authors: Mulvey, L., Sands, W. A., Salin, K., Carr, A. E., and Selman, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
ISSN (Online):1872-8057
Published Online:03 September 2016
Copyright Holders:Copyright © 2016 Elsevier Ireland Ltd.
First Published:First published in Molecular and Cellular Endocrinology 455:41-53
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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