Alternative splicing of coq-2 controls the level of rhodoquinone in animals
- University of Toronto, Canada
- Institut Pasteur de Montevideo, Uruguay
- The University of Tennessee, United States
- Gonzaga University, United States
- University of Colorado School of Medicine, United States
Abstract
Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia they use ubiquinone (UQ), but in the anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change in substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019) - how this substrate choice is made is unknown. Here, we show helminths make two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that make RQ. We show that in C. elegans COQ-2e is required for efficient RQ synthesis and for survival in cyanide. Crucially, parasites switch from COQ-2a to COQ-2e as they transition into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Canadian Institutes of Health Research (501584)
- Andrew G Fraser
Canadian Institutes of Health Research (5003009)
- Andrew G Fraser
Agencia Nacional de Investigación e Innovación (FCE_2014_1_104366)
- Gustavo Salinas
Agencia Nacional de Investigación e Innovación (FCE_1_2019_1_155779)
- Gustavo Salinas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Tan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Alternative splicing of coq-2 controls the level of rhodoquinone in animals
eLife 9:e56376.
https://doi.org/10.7554/eLife.56376
Further reading
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Biological aging exhibits heterogeneity across multi-organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.
Methods:
This study involved 8396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera–Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine the associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.
Results:
About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in HLI showed a protective association with the acceleration of all BAs, with a mean shift of –0.19 (95% CI −0.34, –0.03) in the comprehensive BA acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors, with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.
Conclusions:
Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Funding:
This work was primarily supported by the National Natural Science Foundation of China (Grant No. 82273740) and Sichuan Science and Technology Program (Natural Science Foundation of Sichuan Province, Grant No. 2024NSFSC0552). The CMEC study was funded by the National Key Research and Development Program of China (Grant No. 2017YFC0907305, 2017YFC0907300). The sponsors had no role in the design, analysis, interpretation, or writing of this article.
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Results:
275,896 individuals were diagnosed with real-time polymerase chain reaction-confirmed SARS-CoV-2 infection in April–May 2022; 199,312/275,896 were included in analyses on the effect of a post-infection vaccine dose. Post-infection vaccination provided protection against reinfection (aHR 0.82; 95% confidence interval 0.79–0.85). For patients who had received one, two, or three vaccine doses before their first infection, hazard ratios for the post-infection vaccination effect were 0.84 (0.76–0.93), 0.87 (0.83–0.90), and 0.96 (0.74–1.23), respectively. Post-infection vaccination within 30 and 90 days before the second Omicron wave provided different degrees of protection (in aHR): 0.51 (0.44–0.58) and 0.67 (0.61–0.74), respectively. Moreover, for all vaccine types, but to different extents, a post-infection dose given to individuals who were fully vaccinated before first infection was protective.
Conclusions:
In previously vaccinated and infected individuals, an additional vaccine dose provided protection against Omicron variant reinfection. These observations will inform future policy decisions on COVID-19 vaccination in China and other countries.
Funding:
This study was funded the Key Discipline Program of Pudong New Area Health System (PWZxk2022-25), the Development and Application of Intelligent Epidemic Surveillance and AI Analysis System (21002411400), the Shanghai Public Health System Construction (GWVI-11.2-XD08), the Shanghai Health Commission Key Disciplines (GWVI-11.1-02), the Shanghai Health Commission Clinical Research Program (20214Y0020), the Shanghai Natural Science Foundation (22ZR1414600), and the Shanghai Young Health Talents Program (2022YQ076).
