Regulation of mitochondrial function by a thyroid hormone. Indirect regulation: binding the thyroid hormone tri-iodothyronine (T3) to the T3 receptor (T3R) leads to upregulation of transcriptional regulators of mitochondrial biogenesis, such as NRF-1 and PGC-1α. NRF-1 and PGC-1α then can upregulate transcription of the nuclear-encoded mitochondrial basal transcription machinery (Tfam, Polrmt), which stimulates mitochondrial DNA (mtDNA) replication and mitochondrial biogenesis. Direct regulation: thyroid hormone binds directly to two mitochondrial proteins, the inner mitochondrial membrane adenine nucleotide transporter (AdNT) and a truncated version of T3R located in the mitochondrial matrix. T3 regulates expression from the mitochondrial genome via T3R, which may bind directly to the mitochondrial DNA.