ArticleNature cell biology2022
LONP-1 and ATFS-1 sustain deleterious heteroplasmy by promoting mtDNA replication in dysfunctional mitochondria.
Article in Nature cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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62 citing papers in PubMed, 94 citations in OpenAlex.
- Mitochondrial depolarization stabilizes the vitamin BProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Tumor-derived DNA drives cancer-associated anemia by promoting reticulocyte clearance.Signal transduction and targeted therapy · 2026Article
- Mechanistic insights and therapeutic interventions of mitochondrial quality control in chemotherapy-related cognitive impairment.Neoplasia (New York, N.Y.) · 2026Review
- ALKB-1-dependent tRNA methylation is required for efficient paternal mitochondrial elimination.Nature communications · 2026Article
- Mitochondrial heterogeneity drives the evolution of fungicide resistance inScience advances · 2026Article
- Mitochondrial unfolded protein response as a central stress-integration hub: mechanisms and implications in disease contexts.Burns & trauma · 2026Review
- Genome-wide characterization of theFrontiers in plant science · 2026Article
- Mitochondrial depolarization stabilizes the vitamin B12 chaperone MMADHC in the cytosol to increase MTR activity.bioRxiv : the preprint server for biology · 2025Article
- Model organisms in POLG-related disorders: insights from yeast to multicellular systems.Cell death & disease · 2025Review
- When Mitochondria Falter, the Barrier Fails: Mechanisms of Inner Blood-Retinal Barrier (iBRB) Injury and Opportunities for Mitochondria-Targeted Repair.International journal of molecular sciences · 2025Review
- Identifying a novel Mecp2-mediated epigenetic mechanism controlling Lonp1 in the hippocampus and its disruption by aging.Scientific reports · 2025Article
- Replication competition drives the selective mtDNA inheritance in Drosophila ovary.Cell reports · 2025Article
- Cryo-EM Reveals Regulatory Mechanisms Governing Substrate Selection and Activation of Human LONP1.bioRxiv : the preprint server for biology · 2025Article
- Comparative mitogenomics reveals evolutionary drivers of Strongyloidea nematodes dwelling in gastrointestinal tract.BMC genomics · 2025Article
- Mitochondrial dynamics and quality control regulate proteostasis in neuronal ischemia-reperfusion.Autophagy · 2025Article
- Multidimensional third-generation sequencing of modified DNA bases allows interrogation of complex biological systems.Nature communications · 2025Article
- Mitochondrial dysfunction in the regulation of aging and aging-related diseases.Cell communication and signaling : CCS · 2025Review
- Inheritance bias of deletion-harbouring mtDNA in yeast: The role of copy number and intracellular selection.PLoS genetics · 2025Article
2 more citing papers are in PubMed but not listed here.
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14 authors at 2 institutions in 1 country.
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Abstract
The accumulation of deleterious mitochondrial DNA (∆mtDNA) causes inherited mitochondrial diseases and ageing-associated decline in mitochondrial functions such as oxidative phosphorylation. Following mitochondrial perturbations, the bZIP protein ATFS-1 induces a transcriptional programme to restore mitochondrial function. Paradoxically, ATFS-1 is also required to maintain ∆mtDNAs in heteroplasmic worms. The mechanism by which ATFS-1 promotes ∆mtDNA accumulation relative to wild-type mtDNAs is unclear. Here we show that ATFS-1 accumulates in dysfunctional mitochondria. ATFS-1 is absent in healthy mitochondria owing to degradation by the mtDNA-bound protease LONP-1, which results in the nearly exclusive association between ATFS-1 and ∆mtDNAs in heteroplasmic worms. Moreover, we demonstrate that mitochondrial ATFS-1 promotes the binding of the mtDNA replicative polymerase (POLG) to ∆mtDNAs. Interestingly, inhibition of the mtDNA-bound protease LONP-1 increased ATFS-1 and POLG binding to wild-type mtDNAs. LONP-1 inhibition in Caenorhabditis elegans and human cybrid cells improved the heteroplasmy ratio and restored oxidative phosphorylation. Our findings suggest that ATFS-1 promotes mtDNA replication in dysfunctional mitochondria by promoting POLG-mtDNA binding, which is antagonized by LONP-1.
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