University of London group demonstrates mitonuclear interactions change redox stress responses in fruit flies
Eukaryotes have a distinct cell nucleus that contains one set of genes (DNA), and another entity known as the mitochondrion, that contains its own unique genes. Mitochondria are the cellular hubs for energy production and much of metabolism.
Eukaryotes have a distinct cell nucleus that contains one set of genes (DNA), and another entity known as the mitochondrion, that contains its own unique genes. Mitochondria are the cellular hubs for energy production and much of metabolism.
Proteins that function in the mitochondria are mosaiced from these two different genomes: nuclear and mitochondrial. Incompatibilities between the nuclear and mitochondrial genes can cause issues with the cellular response to redox stress.
The effect, which is called "mitonuclear" interactions, is the subject of a study by researchers at University College London, posted Feb. 10 on the online preprint website bioarXiv. The researchers look at how the stress response varied in different fly lines that were genetically engineered to have small differences in their mitochondrial genomes.
Mitonuclear interactions
Interestingly, the mitochondria do not contain only the proteins that their small genome is able to produce. Rather they are “mosaic assemblies” encoded by both the mitochondrial and nuclear genomes (DNA).
The interaction of these two different genomes is called mitonuclear.
Function of mitochondria
Mitochondria are key to both energy production and metabolism in the eukaryote organism. They are especially vulnerable to changes in oxidation rates.
“Incompatibilities between mitochondrial and nuclear genes can perturb respiration, photosynthesis, signaling and gene expression,” the authors wrote.
In sexually reproducing eukaryotes, the DNA packaged inside the cell nucleus derives from the gene lines of both parents. But the DNA inside the mitochondria, the energy-producing organelle within the cell, is passed down usually from the mother alone.
Earlier studies had shown that subtle differences in the mitochondrial DNA could occur as a result of sexual reproduction.
Response to NAC stress
In this study the researchers looked at how the cell’s response to an excess of reactive oxygen species varied in three different lineages of fruit flies (Drosophila melanogaster).
The flies were genetically engineered to have small differences in their mitochondrial genomes. Then they were exposed to N-acetyl cysteine (NAC), an amino acid usually considered an antioxidant.
The NAC exposure “caused infertility and high mortality in some groups but not others,” the authors reported. There were dramatic differences in survival rate between males and females, depending on the dose of NAC.
The high mortality rate in certain female lines was associated with severe suppression of an important chemical pathway for respiration. The authors suspect that the suppression of this chemical pathway, known as complex I, may be more pronounced in female flies due to the high metabolic costs of egg production.
“While our interpretation of respiratory suppression and redox balance has not been proved here, there is no doubt that subtle differences in mitonuclear genotype can induce extreme differences in responses to redox stress through NAC supplementation,” the authors concluded.
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M. Florencia Camus et al. Mitonuclear interactions produce extreme differences in response to redox stress. bioarXiv (2022).
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