How is mitochondrial DNA (mtDNA) expression regulated?

mtDNA expression is primarily regulated by nuclear-encoded transcription factors that bind to specific sequences in the mitochondrial genome. These transcription factors include: T3 receptor p43, CREB, p53 activator of transcription 3 (Stat3), signal transducer and the estrogen receptor. T3R (activated by thyroid hormone T3) regulates mitochondrial biogenesis indirectly by stimulating the expression of nuclear genes involved in mitochondrial function. p53, known for its role in apoptosis and DNA repair, also regulates mitochondrial DNA maintenance and repair. Stat3, known for its nuclear functions in transcriptional responses, is also found in mitochondria. It mediates mitochondrial function by interacting with the respiratory electron transport chain. Estrogen receptor (activated by estrogen) is localized in mitochondria and regulates mitochondrial gene expression. CREB binds to CREs in mitochondrial DNA and regulates mitochondrial gene expression.