Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function

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Science Signaling  26 Jun 2018:
Vol. 11, Issue 536, eaam5855
DOI: 10.1126/scisignal.aam5855

Two nuclear receptors for mitochondria

Mitochondrial processes such as fission, mitophagy, and biogenesis are regulated by thyroid hormone receptor (THR) and ERRα, both of which are nuclear receptors that alter gene expression when bound to ligand. Noting that many THR target genes lack response elements for this nuclear receptor, Singh et al. investigated the regulation of genes involved in mitochondrial pathways by THR. Using a human liver cell line and mice treated with TH in the absence or presence of an ERRα inhibitor, the authors found that THR mediated its effects on mitochondrial processes by increasing the expression of the gene encoding ERRα. These results suggest that agonist activation of ERRα could be used to improve mitochondrial quality in metabolic or neurodegenerative diseases or aging.

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