ArticleNucleic acids research2023
Two mitochondrial HMG-box proteins, Cim1 and Abf2, antagonistically regulate mtDNA copy number in Saccharomyces cerevisiae.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 17 citations in OpenAlex.
- Experimental evolution of cellular miniaturization reveals a putative mechanism for cell size evolution.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional characterization of HMG_9 and CMicrobial cell factories · 2026Article
- Mrx6 binds the Lon protease Pim1 N-terminal domain to confer selective substrate specificity and regulate mtDNA copy number.Nucleic acids research · 2026Article
- Local mitochondrial physiology defined by mtDNA quality guides purifying selection.PLoS genetics · 2026Article
- Article
- Ecm19 coordinates mitochondrial fission and cellular redox homeostasis.Redox report : communications in free radical research · 2025Article
- When HSFs bring the heat-mapping the transcriptional circuitries of HSF-type regulators inmSphere · 2025Review
- Epigenetic Threads of Neurodegeneration: TFAM's Intricate Role in Mitochondrial Transcription.CNS & neurological disorders drug targets · 2025Review
- Significantly reduced, but balanced, rates of mitochondrial fission and fusion are sufficient to maintain the integrity of yeast mitochondrial DNA.Molecular biology of the cell · 2024Article
- Real-time assessment of mitochondrial DNA heteroplasmy dynamics at the single-cell level.The EMBO journal · 2024Article
- Flow-cytometry reveals mitochondrial DNA accumulation inFrontiers in cell and developmental biology · 2024Article
- Spontaneous Mutations inInternational journal of molecular sciences · 2023Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The mitochondrial genome, mtDNA, is present in multiple copies in cells and encodes essential subunits of oxidative phosphorylation complexes. mtDNA levels have to change in response to metabolic demands and copy number alterations are implicated in various diseases. The mitochondrial HMG-box proteins Abf2 in yeast and TFAM in mammals are critical for mtDNA maintenance and packaging and have been linked to mtDNA copy number control. Here, we discover the previously unrecognized mitochondrial HMG-box protein Cim1 (copy number influence on mtDNA) in Saccharomyces cerevisiae, which exhibits metabolic state dependent mtDNA association. Surprisingly, in contrast to Abf2's supportive role in mtDNA maintenance, Cim1 negatively regulates mtDNA copy number. Cells lacking Cim1 display increased mtDNA levels and enhanced mitochondrial function, while Cim1 overexpression results in mtDNA loss. Intriguingly, Cim1 deletion alleviates mtDNA maintenance defects associated with loss of Abf2, while defects caused by Cim1 overexpression are mitigated by simultaneous overexpression of Abf2. Moreover, we find that the conserved LON protease Pim1 is essential to maintain low Cim1 levels, thereby preventing its accumulation and concomitant repressive effects on mtDNA. We propose a model in which the protein ratio of antagonistically acting Cim1 and Abf2 determines mtDNA copy number.
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