Study uncovers mitonuclear effects on redox stress response in drosophila

A recent study explores the influence of mild mitonuclear incompatibilities on Drosophila's response to N-acetyl cysteine (NAC)-induced redox stress. The report from May 2023 highlighted how NAC's impact varies with factors such as mitonuclear genotype, gender, and tissue, demonstrating that complex I-linked respiration suppression is a crucial factor in mitigating redox stress, occasionally resulting in mortality.

According to the study published in ScienceDirect, researchers have delved into the impact of mild mitonuclear incompatibilities on the body's response to redox stress induced by N-acetyl cysteine (NAC). In this study, three distinct Drosophila melanogaster lines, featuring mitochondrial genomes that were either coevolved (WT) or mildly mismatched (BAR, COX) to a consistent nuclear background, were investigated. Results revealed significant variations in responses to NAC, dependent on factors like mitonuclear genotype, gender, tissue type, and dosage.

The report said that NAC exhibited contrasting effects, causing infertility and high mortality in specific groups, while leaving others unaffected. Using precise tissue-specific fluorespirometry, the research demonstrated that NAC did not alter H2O2 flux but notably suppressed complex I-linked respiration, particularly in female flies, while sustaining a reduced glutathione pool. The study further identified that the high mortality observed in BAR females was closely tied to substantial (>50%) complex I-linked respiration suppression, along with increased H2O2 flux in the ovaries and notable glutathione pool oxidation.

The findings from this research suggest that the attenuation of redox stress is intrinsically connected to the suppression of complex I-linked respiration, with certain mitonuclear lines even experiencing fatal consequences. This observation leads to the proposed hypothesis that the suppression of complex I-linked respiration serves as a general mechanism for preserving redox balance in tissues. Such an adaptation may play a pivotal role in mitigating the oxidative stress associated with aging, thereby influencing metabolic changes and potentially triggering age-related declines linked to epigenetic modifications.

ScienceDirect: M. Florencia Camus, et al. Redox stress shortens lifespan through suppression of respiratory complex I in flies with mitonuclear incompatibilities. Experimental Gerontology (May 2023). DOI: https://doi.org/10.1016/j.exger.2023.112158