Tissue-specific heteroplasmy dynamics is accompanied by a sharp drop in mtDNA copy number during development
Tsyba, N.; Patel, M. R.
Show abstract
Mitochondrial mutation phenotypes are highly unpredictable as they depend on 3 variables; mutant-to-wildtype ratio (heteroplasmy level), total number of mitochondrial genomes (mtDNA), and the tissue affected. The exact phenotype experienced is governed by the combination of these variables, but current models lack the capability to examine the three variables simultaneously. We have established a C. elegans muscle and neuron system to overcome this challenge. Using this system, we measure heteroplasmy level and mtDNA copy number throughout development. Our results show that neurons accumulate significantly higher heteroplasmy level than muscles. These tissue-specific differences arise late in development, and are dependent on AMP-activated protein kinase (AMPK). Importantly, we find that somatic tissues lose more than half of their mtDNA content during development. These findings show that heteroplasmy levels can remain stable, or even increase, despite acute mtDNA losses.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Nucleolar stress in Drosophila neuroblasts, a model for human ribosomopathies 95%
- Genetic analysis of C. elegans Haspin-like genes shows that hasp-1 plays multiple roles in the germline 95%
- The Drosophila orthologue of the primary ciliary dyskinesia-associated gene, DNAAF3, is required for axonemal dynein assembly 94%
Similar papers in this journal
- Distinct mechanoreceptor pezo-1 isoforms modulate food intake in the nematode Caenorhabditis elegans 96%
- Escherichia coli Metabolite Profiling Leads to the Development of an RNA Interference Strain for Caenorhabditis elegans 96%
- Conditional immobilization for live imaging C. elegans using auxin-dependent protein depletion 95%
Similar papers in this journal
- Measuring nucleus mechanics within a living multicellular organism: Physical decoupling and attenuated recovery rate are physiological protective mechanisms of the cell nucleus under high mechanical load 94%
- Basal autophagy during meiotic prophase I is required for accurate chromosome segregation in Drosophila oocytes and declines during oocyte aging 94%
- Mitochondria regulate Drosophila intestinal stem cell differentiation through FOXO 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.