ArticleLife science alliance2021
High levels of TFAM repress mammalian mitochondrial DNA transcription in vivo.
Article in Life science alliance, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Sperm mitochondrial DNA copy number: a marker of male fertility and reproductive success.Human reproduction update · 2026Review
- Reprogramming Mitochondrial Adaptation: LONP1 at the Crossroads of Proteostasis, Metabolism, and Disease.Antioxidants (Basel, Switzerland) · 2026Review
- CRISPR-Cas-based activation of PPARGC1A boosts endogenous mitochondria and enhances cardiac function after myocardial infarction.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Role of mitochondrial translation in modulating inflammatory disease outcome: Current knowledge and future perspectives.The Journal of biological chemistry · 2026Review
- Metabolic Myokines and Adipokines in the Follicular Microenvironment: Implications for Oocyte Competence and IVF Outcomes.International journal of molecular sciences · 2026Review
- Integrative Proteomic and Bioenergetic Profiling Reveals Diet- and Strain-Specific Mitochondrial Dysfunction in Cohen Diabetic Rat Hearts.Antioxidants (Basel, Switzerland) · 2026Article
- Cooperative Architecture of Mitochondrial Proteome Homeostasis.medRxiv : the preprint server for health sciences · 2026Article
- Article
- Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development.Journal of cardiovascular development and disease · 2026Review
- Mitophagy and oxidative stress in chronic kidney disease (Review).Molecular medicine reports · 2026Review
- The role of mitochondrial proteases in inflammation and immunity.Frontiers in immunology · 2026Review
- Aldosterone increases the expression and subcellular localization of SERCA2a and SERCA2b in the rat mesenteric artery.Frontiers in physiology · 2026Article
- POLRMT overexpression increases mtDNA transcription without affecting steady-state mRNA levels.Life science alliance · 2025Article
- Imbalance in MICOS Proteins in Rat Liver Mitochondria in an Induced Hyperthyroidism Model.Cells · 2025Article
- The bottleneck for maternal transmission of mtDNA is linked to purifying selection by autophagy.Science advances · 2025Article
- Molecular mechanisms and functions of protein acetylation in sepsis and sepsis-associated organ dysfunction.Cellular & molecular biology letters · 2025Review
- Tissue-specific responses to TFAM and mtDNA copy number manipulation in prematurely ageing mice.eLife · 2025Article
- DJ-1 deficiency and aging: dual drivers of retinal mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2025Article
- Activating AMPK improves pathological phenotypes due to mtDNA depletion.The FEBS journal · 2025Article
- Spatial analysis of mitochondrial gene expression reveals dynamic translation hubs and remodeling in stress.Science advances · 2025Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial transcription factor A (TFAM) is compacting mitochondrial DNA (dmtDNA) into nucleoids and directly controls mtDNA copy number. Here, we show that the TFAM-to-mtDNA ratio is critical for maintaining normal mtDNA expression in different mouse tissues. Moderately increased TFAM protein levels increase mtDNA copy number but a normal TFAM-to-mtDNA ratio is maintained resulting in unaltered mtDNA expression and normal whole animal metabolism. Mice ubiquitously expressing very high TFAM levels develop pathology leading to deficient oxidative phosphorylation (OXPHOS) and early postnatal lethality. The TFAM-to-mtDNA ratio varies widely between tissues in these mice and is very high in skeletal muscle leading to strong repression of mtDNA expression and OXPHOS deficiency. In the heart, increased mtDNA copy number results in a near normal TFAM-to-mtDNA ratio and maintained OXPHOS capacity. In liver, induction of LONP1 protease and mitochondrial RNA polymerase expression counteracts the silencing effect of high TFAM levels. TFAM thus acts as a general repressor of mtDNA expression and this effect can be counterbalanced by tissue-specific expression of regulatory factors.
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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.