ArticleNucleic acids research2018
Acetylation and phosphorylation of human TFAM regulate TFAM-DNA interactions via contrasting mechanisms.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- Concurrent positional dynamics and activity mapping of DNA-binding proteins.Nature protocols · 2026Review
- PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.Nature communications · 2026Article
- Epigenetic and mitoepigenetic regulation in cancer and therapeutic perspectives.Frontiers in pharmacology · 2026Review
- Discovery of a novel Nrf2 activator that modulates mitochondrial function in neurons by regulating DHRS3-Nrf2 interaction after ischemic stroke.Theranostics · 2026Article
- SNAP23 deficiency triggers Trim21 mitochondrial translocation to suppress TFAM-mediated oxidative metabolism and drive chemoresistance in colorectal cancer.Cell death & disease · 2025Article
- Exploring the connection between the Mitochondrial DNA and the Circadian Rhythm: Insights into Mitochondrial Biogenesis and its Dynamics.Molecular biology reports · 2025Review
- Mitoepigenetic Targeting of Age-Related Dysfunction: Mechanisms, Therapeutic Avenues, and Transgenerational Implications.Aging advances · 2025Article
- Platelet methyltransferase-like protein 4-mediated mitochondrial DNA metabolic disorder exacerbates oral mucosal immunopathology in hypoxia.International journal of oral science · 2025Article
- Mitochondria-localized MBD2c facilitates mtDNA transcription and drug resistance.Nature chemical biology · 2025Article
- Mitochondrial epigenetic mechanisms in cancer: an updated overview.Frontiers in cell and developmental biology · 2025Review
- Deregulation of mitochondrial gene expression in cancer: mechanisms and therapeutic opportunities.British journal of cancer · 2024Review
- Biomolecular condensates and disease pathogenesis.Science China. Life sciences · 2024Review
- The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- SUCLG1 restricts POLRMT succinylation to enhance mitochondrial biogenesis and leukemia progression.The EMBO journal · 2024Article
- Single-nucleoid architecture reveals heterogeneous packaging of mitochondrial DNA.Nature structural & molecular biology · 2024Article
- Integrating mitoepigenetics into research in mood disorders: a state-of-the-art review.Frontiers in physiology · 2024Review
- Article
- Key Amino Acid Residues of Mitochondrial Transcription Factor A Synergize with Abasic (AP) Site Dynamics To Facilitate AP-Lyase Reactions.ACS chemical biology · 2023Article
- New insights into the pathophysiology of methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- Assessing TFAM Binding to Human Mitochondrial DNA.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Mitochondrial transcription factor A (TFAM) is essential for the maintenance, expression and transmission of mitochondrial DNA (mtDNA). However, mechanisms for the post-translational regulation of TFAM are poorly understood. Here, we show that TFAM is lysine acetylated within its high-mobility-group box 1, a domain that can also be serine phosphorylated. Using bulk and single-molecule methods, we demonstrate that site-specific phosphoserine and acetyl-lysine mimics of human TFAM regulate its interaction with non-specific DNA through distinct kinetic pathways. We show that higher protein concentrations of both TFAM mimics are required to compact DNA to a similar extent as the wild-type. Compaction is thought to be crucial for regulating mtDNA segregation and expression. Moreover, we reveal that the reduced DNA binding affinity of the acetyl-lysine mimic arises from a lower on-rate, whereas the phosphoserine mimic displays both a decreased on-rate and an increased off-rate. Strikingly, the increased off-rate of the phosphoserine mimic is coupled to a significantly faster diffusion of TFAM on DNA. These findings indicate that acetylation and phosphorylation of TFAM can fine-tune TFAM-DNA binding affinity, to permit the discrete regulation of mtDNA dynamics. Furthermore, our results suggest that phosphorylation could additionally regulate transcription by altering the ability of TFAM to locate promoter sites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.