Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21


ABSTRACT: Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with mitochondrial perturbations in SM, triggering an increased protein turnover and amino acid metabolism with induced biosynthetic serine/1-carbon/glycine pathway and the longevity-promoting polyamine spermidine as well as the trans-sulfuration pathway. This is related to an induction of NADPH-generating pathways and glutathione metabolism as an adaptive mitohormetic response and defense against increased oxidative stress. Strikingly, consistent muscle retrograde signaling profiles were observed in acute stress states such as muscle cell starvation and lipid overload, muscle regeneration, and heart muscle inflammation, but not in response to exercise. We provide conclusive evidence for a key compensatory stress-signaling network that preserves cellular function, oxidative stress tolerance, and survival during conditions of increased SM mitochondrial distress, a metabolic reprogramming profile so far only demonstrated for cancer cells and heart muscle.-Ost, M., Keipert, S., van Schothorst, E. M., Donner, V., van der Stelt, I., Kipp, A. P., Petzke, K.-J., Jove, M., Pamplona, R., Portero-Otin, M., Keijer, J., and Klaus, S. Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux. Control C57BL/6J wildtype male mice, aged 12 weeks, are compared to UCP1 transgene littermates fed purified low fat diet (BIOCLAIMS, Hoevenaars et al., Genes and Nutrition 2012) for 12 weeks . At the end, mice were sacrificed, gastrocnemius skeletal muscle was immediately dissected and snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 8x60K microarrays. In total, 6 arrays of individual WT and 7 arrays of individual UCP1-TG samples were normalized, together with samples from the complete SUPERSERIES.

ORGANISM(S): Mus musculus

SUBMITTER: Evert van Schothorst 

PROVIDER: E-GEOD-45991 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Muscle mitohormesis promotes cellular survival via serine/glycine pathway flux.

Ost Mario M   Keipert Susanne S   van Schothorst Evert M EM   Donner Verena V   van der Stelt Inge I   Kipp Anna P AP   Petzke Klaus-Jürgen KJ   Jove Mariona M   Pamplona Reinald R   Portero-Otin Manuel M   Keijer Jaap J   Klaus Susanne S  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20141209 4


Recent studies on mouse and human skeletal muscle (SM) demonstrated the important link between mitochondrial function and the cellular metabolic adaptation. To identify key compensatory molecular mechanisms in response to chronic mitochondrial distress, we analyzed mice with ectopic SM respiratory uncoupling in uncoupling protein 1 transgenic (UCP1-TG) mice as model of muscle-specific compromised mitochondrial function. Here we describe a detailed metabolic reprogramming profile associated with  ...[more]

Similar Datasets

2015-02-17 | GSE45991 | GEO
2023-05-01 | GSE205194 | GEO
2016-01-07 | E-GEOD-71749 | biostudies-arrayexpress
2012-07-23 | E-GEOD-39562 | biostudies-arrayexpress
2016-10-03 | GSE79031 | GEO
2012-07-24 | GSE39562 | GEO
2021-06-05 | GSE164964 | GEO
2024-10-30 | GSE267959 | GEO
2019-12-01 | GSE138264 | GEO
2018-03-01 | GSE109829 | GEO