@article{9359a9735e804ce2943fb6d863a45b35,
title = "Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function",
abstract = "Mitochondrial dysfunction is a key driver of diabetes and other metabolic diseases. Mitochondrial redox state is highly impactful to metabolic function but the mechanism driving this is unclear. We generated a transgenic mouse which overexpressed the redox enzyme Thioredoxin Reductase 2 (TrxR2), the rate limiting enzyme in the mitochondrial thioredoxin system. We found augmentation of TrxR2 to enhance metabolism in mice under a normal diet and to increase resistance to high-fat diet induced metabolic dysfunction by both increasing glucose tolerance and decreasing fat deposition. We show this to be caused by increased mitochondrial function which is driven at least in part by enhancements to the tricarboxylic acid cycle and electron transport chain function. Our findings demonstrate a role for TrxR2 and mitochondrial thioredoxin as metabolic regulators and show a critical role for redox enzymes in controlling functionality of key mitochondrial metabolic systems.",
author = "Chocron, {E. Sandra} and Kennedy Mdaki and Nisi Jiang and Jodie Cropper and Pickering, {Andrew M.}",
note = "Funding Information: We want to thank the pathology core at UT Health San Antonio for helping with tissue processing services. We wish to thank Dr. Exing Wang from the Optical Imaging core at UTHSA for help with analysis of oil red O images. We thank Melissa J Sammy, Ph.D. and Kelley Smith-Johnston, B.S. at the UAB Bioanalytical Redox Biology (BARB) Core, Diabetes Research Center (NIDDK DK P30DK079626), NORC (NIDDK DK056336), UCEM, UCDC, CFRB, and UCNC for performing the seahorse experiments. This research was supported by NIA/NIH R56 AG061051, Glenn Foundation for Medical Research, and AFAR Grants for Junior Faculty, Voelcker Young Investigator Award, San Antonio Nathan Shock Center, San Antonio Pepper Center. All animal procedures were approved under IACUC 20170040AR. Mouse artwork is used under the Creative Commons license: commons.wikimedia.org/wiki/File:Vector_diagram_of_laboratory_mouse_(black_and_white).svg. Funding Information: We want to thank the pathology core at UT Health San Antonio for helping with tissue processing services. We wish to thank Dr. Exing Wang from the Optical Imaging core at UTHSA for help with analysis of oil red O images. We thank Melissa J Sammy, Ph.D. and Kelley Smith-Johnston, B.S. at the UAB Bioanalytical Redox Biology (BARB) Core, Diabetes Research Center (NIDDK DK P30DK079626), NORC (NIDDK DK056336), UCEM, UCDC, CFRB, and UCNC for performing the seahorse experiments. This research was supported by NIA/NIH R56 AG061051, Glenn Foundation for Medical Research, and AFAR Grants for Junior Faculty, Voelcker Young Investigator Award, San Antonio Nathan Shock Center, San Antonio Pepper Center. All animal procedures were approved under IACUC 20170040AR. Mouse artwork is used under the Creative Commons license: commons.wikimedia.org/wiki/File:Vector_diagram_of_laboratory_mouse_(black_and_white).svg. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s42003-022-03405-w",
language = "English (US)",
volume = "5",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}