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. 2024 Jul;598(14):1715-1729.
doi: 10.1002/1873-3468.14942. Epub 2024 Jun 2.

Nuclear receptor Nur77 and Yin-Yang 1 synergistically increase mitochondrial abundance and activity in macrophages

Duco S Koenis  1   2   3 , Inkie J A Evers-van Gogh  4 , Pieter B van Loenen  1   2   3 , Wilbert Zwart  5 , Eric Kalkhoven  4 , Carlie J M de Vries  1   2   3
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Free article

Nuclear receptor Nur77 and Yin-Yang 1 synergistically increase mitochondrial abundance and activity in macrophages

Duco S Koenis et al. FEBS Lett. 2024 Jul.
Free article

Abstract

Mitochondrial biogenesis requires precise regulation of both mitochondrial-encoded and nuclear-encoded genes. Nuclear receptor Nur77 is known to regulate mitochondrial metabolism in macrophages and skeletal muscle. Here, we compared genome-wide Nur77 binding site and target gene expression in these two cell types, which revealed conserved regulation of mitochondrial genes and enrichment of motifs for the transcription factor Yin-Yang 1 (YY1). We show that Nur77 and YY1 interact, that YY1 increases Nur77 activity, and that their binding sites are co-enriched at mitochondrial ribosomal protein gene loci in macrophages. Nur77 and YY1 co-expression synergistically increases Mrpl1 expression as well as mitochondrial abundance and activity in macrophages but not skeletal muscle. As such, we identify a macrophage-specific Nur77-YY1 interaction that enhances mitochondrial metabolism.

Keywords: macrophage; mitochondria; nuclear receptor; skeletal muscle; transcriptional regulation.

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