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Updated: Dec 23, 2025
Unveiling Xenobiotic Transport and Effects in Isolated Mitochondria: Insights from Respirometric and Enzymatic Assays
Published on: March 7, 2025
Transcriptomic analysis reveals common pathways and biomarkers associated with oxidative damage caused by
Fenghua Wei1, Tenghui Su2, Dali Wang2
1State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou, 510640, China; Guangdong Key Laboratory of Environmental Pollution and Health, School of Environment, Jinan University, Guangzhou, 511443, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
Abstract:
A variety of chemicals are capable of provoking mitochondrial dysfunction and thereby contribute to metabolic disorder related effects in wildlife and human. For better identifying new mitochondrial toxicants and assessing mitochondria-related risk, an in-depth understanding of toxic mechanisms and biomarkers should be attained. In the current study, a representative mitotoxicant, azoxystrobin, was assessed for lethal and sublethal outcomes in Chironomus dilutus after 96-h exposure and the toxic mechanism was explored. Global transcriptomic profiles by RNA-sequencing revealed that ampk, acc1, atp2a, gsk3b, pi3k, fak, atr, chk1, and map3k5 were the key genes which involved in the toxic action of azoxystrobin and could serve as potential molecular biomarkers. A major network of common toxicity pathways was then developed for mitotoxicants towards aquatic insects. In particular, calcium ion-PI3K/AKT and cAMP-AMPK-lethality pathways were demonstrated, in addition to the well-known mitochondrial electron transfer-oxidative damage-apoptosis pathway. These analyses could help developing adverse outcome pathways that integrate toxicological information at various levels and support more effective risk assessment and management of mitotoxicants.
Insights
This study identifies key genes and pathways affected by the mitotoxicant azoxystrobin in aquatic insects. Understanding these molecular biomarkers aids in assessing risks from mitochondrial toxicants.
Area of Science:
- Environmental Toxicology
- Molecular Biology
- Biomarker Discovery
Background:
- Chemicals can cause mitochondrial dysfunction, leading to metabolic disorders in wildlife and humans.
- Identifying mitochondrial toxicants and understanding their mechanisms are crucial for risk assessment.
Purpose of the Study:
- To investigate the toxic effects and mechanisms of azoxystrobin, a known mitotoxicant, in Chironomus dilutus.
- To identify potential molecular biomarkers for assessing mitochondria-related risks.
Main Methods:
- Exposure of Chironomus dilutus to azoxystrobin for 96 hours.
- Analysis of lethal and sublethal outcomes.
- Global transcriptomic profiling using RNA-sequencing.
Main Results:
- Azoxystrobin exposure led to significant changes in key genes (ampk, acc1, atp2a, gsk3b, pi3k, fak, atr, chk1, map3k5).
- These genes are identified as potential molecular biomarkers for azoxystrobin toxicity.
- New toxicity pathways, including calcium ion-PI3K/AKT and cAMP-AMPK-lethality, were elucidated alongside the mitochondrial electron transfer-oxidative damage-apoptosis pathway.
Conclusions:
- The identified genes and pathways provide insights into the toxic action of azoxystrobin and other mitotoxicants.
- This research supports the development of adverse outcome pathways for improved risk assessment and management of mitochondrial toxicants in aquatic ecosystems.
