Mitochondrial TrxR2 regulates metabolism and protects from metabolic disease through enhanced TCA and ETC function

Communications Biology - Tập 5 Số 1
E. Sandra Chocrón1, Kennedy S. Mdaki1, Nisi Jiang1, Jodie Cropper1, Andrew M. Pickering2
1Barshop Institute for Longevity and Aging Studies, University of Texas Health, San Antonio, San Antonio, TX, USA
2Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA

Tóm tắt

AbstractMitochondrial 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.

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Communications Biology

Tập 5 Số 1

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