ArticleMolecular cell2013
Phosphorylation of human TFAM in mitochondria impairs DNA binding and promotes degradation by the AAA+ Lon protease.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers.
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Who cites it
189 citing papers in PubMed, 317 citations in OpenAlex.
- A selective inhibitor reveals roles for LONP1 in mitochondrial proteostasis and OXPHOS dependencies.Life science alliance · 2026Article
- Ionomycin suppresses cancer cell growth by disrupting mitochondrial transcription.FEBS open bio · 2026Article
- Sperm mitochondrial DNA copy number: a marker of male fertility and reproductive success.Human reproduction update · 2026Review
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Reprogramming Mitochondrial Adaptation: LONP1 at the Crossroads of Proteostasis, Metabolism, and Disease.Antioxidants (Basel, Switzerland) · 2026Review
- TFAM promotes mitochondrial division by increasing mitochondrial Sirt3.Cell death & disease · 2026Article
- Molecular mechanisms of mitochondrial AAA+ proteases.The Journal of biological chemistry · 2026Review
- PRMT5 in mitochondria regulates mtDNA stability through TFAM arginine methylation.Nature communications · 2026Article
- Article
- Reversible arginine methylation regulates mitochondrial IDH2 activity: coordinated control by CARM1 and KDM3A/4A.Cell death & disease · 2026Article
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Mrx6 binds the Lon protease Pim1 N-terminal domain to confer selective substrate specificity and regulate mtDNA copy number.Nucleic acids research · 2026Article
- Mitochondrial transcription factor A: linking mtDNA maintenance, mitochondrial stress responses, and inflammaging.Frontiers in aging · 2026Review
- Mitochondrial dysfunction-driven PANoptosis in doxorubicin-induced cardiotoxicity: mechanistic insights and intervention strategies.Frontiers in pharmacology · 2026Review
- Identifying a novel Mecp2-mediated epigenetic mechanism controlling Lonp1 in the hippocampus and its disruption by aging.Scientific reports · 2025Article
- Lon/Pim1-mediated degradation of presequence translocase-associated motor components Pam16 and Pam18 in Saccharomyces cerevisiae.The Biochemical journal · 2025Article
- Harnessing mitochondrial biogenesis to combat acute kidney injury: Current insights and futuredirections.Genes & diseases · 2025Review
- Mitochondrial quality control in cardiomyocytes: safeguarding the heart against disease and ageing.Nature reviews. Cardiology · 2025Review
- Lon-dependent proteolysis in oxidative stress responses.Journal of bacteriology · 2025Review
- IL-21 Loading CaMnCOSmall (Weinheim an der Bergstrasse, Germany) · 2025Article
129 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Human mitochondrial transcription factor A (TFAM) is a high-mobility group (HMG) protein at the nexus of mitochondrial DNA (mtDNA) replication, transcription, and inheritance. Little is known about the mechanisms underlying its posttranslational regulation. Here, we demonstrate that TFAM is phosphorylated within its HMG box 1 (HMG1) by cAMP-dependent protein kinase in mitochondria. HMG1 phosphorylation impairs the ability of TFAM to bind DNA and to activate transcription. We show that only DNA-free TFAM is degraded by the Lon protease, which is inhibited by the anticancer drug bortezomib. In cells with normal mtDNA levels, HMG1-phosphorylated TFAM is degraded by Lon. However, in cells with severe mtDNA deficits, nonphosphorylated TFAM is also degraded, as it is DNA free. Depleting Lon in these cells increases levels of TFAM and upregulates mtDNA content, albeit transiently. Phosphorylation and proteolysis thus provide mechanisms for rapid fine-tuning of TFAM function and abundance in mitochondria, which are crucial for maintaining and expressing mtDNA.
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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.