Imperial College London
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ProfessorJulianGriffin

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3220julian.griffin

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Senyilmaz:2015:10.1038/nature14601,
author = {Senyilmaz, D and Virtue, S and Xu, X and Tan, CY and Griffin, JL and Miller, AK and Vidal-Puig, A and Teleman, AA},
doi = {10.1038/nature14601},
journal = {Nature},
pages = {124--128},
title = {Regulation of mitochondrial morphology and function by stearoylation of TFR1},
url = {http://dx.doi.org/10.1038/nature14601},
volume = {525},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Mitochondria are involved in a variety of cellular functions, including ATP production, amino acid and lipid biogenesis and breakdown, signalling and apoptosis. Mitochondrial dysfunction has been linked to neurodegenerative diseases, cancer and ageing. Although transcriptional mechanisms that regulate mitochondrial abundance are known, comparatively little is known about how mitochondrial function is regulated. Here we identify the metabolite stearic acid (C18:0) and human transferrin receptor 1 (TFR1; also known as TFRC) as mitochondrial regulators. We elucidate a signalling pathway whereby C18:0 stearoylates TFR1, thereby inhibiting its activation of JNK signalling. This leads to reduced ubiquitination of mitofusin via HUWE1, thereby promoting mitochondrial fusion and function. We find that animal cells are poised to respond to both increases and decreases in C18:0 levels, with increased C18:0 dietary intake boosting mitochondrial fusion in vivo. Intriguingly, dietary C18:0 supplementation can counteract the mitochondrial dysfunction caused by genetic defects such as loss of the Parkinson's disease genes Pink or Parkin in Drosophila. This work identifies the metabolite C18:0 as a signalling molecule regulating mitochondrial function in response to diet.
AU  - Senyilmaz,D
AU  - Virtue,S
AU  - Xu,X
AU  - Tan,CY
AU  - Griffin,JL
AU  - Miller,AK
AU  - Vidal-Puig,A
AU  - Teleman,AA
DO  - 10.1038/nature14601
EP  - 128
PY  - 2015///
SN  - 0028-0836
SP  - 124
TI  - Regulation of mitochondrial morphology and function by stearoylation of TFR1
T2  - Nature
UR  - http://dx.doi.org/10.1038/nature14601
UR  - https://www.ncbi.nlm.nih.gov/pubmed/26214738
UR  - http://hdl.handle.net/10044/1/81808
VL  - 525
ER  -
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