ArticleMolecular biology of the cell2015
Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Replication competition drives the selective mtDNA inheritance in Drosophila ovary.Cell reports · 2025Article
- Progressive mitochondrial dysfunction impairs visual signal transduction and induces retinal degeneration inFrontiers in insect science · 2025Article
- A transcription network underlies the dual genomic coordination of mitochondrial biogenesis.eLife · 2024Article
- A transcription network underlies the dual genomic coordination of mitochondrial biogenesis.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial Dysfunctions: Genetic and Cellular Implications Revealed by Various Model Organisms.Genes · 2024Review
- Two mitochondrial DNA polymorphisms modulate cardiolipin binding and lead to synthetic lethality.Nature communications · 2024Article
- Review
- PRKN/parkin-mediated mitophagy is induced by the probioticsAutophagy · 2023Article
- An AI-guided screen identifies probucol as an enhancer of mitophagy through modulation of lipid droplets.PLoS biology · 2023Article
- Article
- Creation of Mitochondrial Disease Models Using Mitochondrial DNA Editing.Biomedicines · 2023Review
- Insights fromFrontiers in neuroscience · 2023Review
- Mitochondrial respiration and dynamics of in vivo neural stem cells.Development (Cambridge, England) · 2022Article
- Mitigation of age-dependent accumulation of defective mitochondrial genomes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The PPR domain of mitochondrial RNA polymerase is an exoribonuclease required for mtDNA replication in Drosophila melanogaster.Nature cell biology · 2022Article
- Mitochondrial DNA heteroplasmy is modulated during oocyte development propagating mutation transmission.Science advances · 2021Article
- Mitochondrial function in development and disease.Disease models & mechanisms · 2021Review
- A versatile toolkit for CRISPR-Cas13-based RNA manipulation in Drosophila.Genome biology · 2020Article
- Mitochondrial DNA segregation and replication restrict the transmission of detrimental mutation.The Journal of cell biology · 2020Article
- Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO.Molecular biology of the cell · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Various human diseases are associated with mitochondrial DNA (mtDNA) mutations, but heteroplasmy—the coexistence of mutant and wild-type mtDNA—complicates their study. We previously isolated a temperature-lethal mtDNA mutation in Drosophila, mt:CoI(T300I), which affects the cytochrome c oxidase subunit I (CoI) locus. In the present study, we found that the decrease in cytochrome c oxidase (COX) activity was ascribable to a temperature-dependent destabilization of cytochrome a heme. Consistently, the viability of homoplasmic flies at 29°C was fully restored by expressing an alternative oxidase, which specifically bypasses the cytochrome chains. Heteroplasmic flies are fully viable and were used to explore the age-related and tissue-specific phenotypes of mt:CoI(T300I). The proportion of mt:CoI(T300I) genome remained constant in somatic tissues along the aging process, suggesting a lack of quality control mechanism to remove defective mitochondria containing a deleterious mtDNA mutation. Using a genetic scheme that expresses a mitochondrially targeted restriction enzyme to induce tissue-specific homoplasmy in heteroplasmic flies, we found that mt:CoI(T300I) homoplasmy in the eye caused severe neurodegeneration at 29°C. Degeneration was suppressed by improving mitochondrial Ca(2+) uptake, suggesting that Ca(2+) mishandling contributed to mt:CoI(T300I) pathogenesis. Our results demonstrate a novel approach for Drosophila mtDNA genetics and its application in modeling mtDNA diseases.
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