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Du 2016 Thesis

From Bioblast
Publications in the MiPMap
Du X (2016) Anthropogenic pollution effects on mitochondrial energy metabolism, gene expression, and genotypes of natural Fundulus heteroclitus populations. Dissertation p175.

» Open Access

Du X (2016) Dissertation

Abstract: Energy balance is a major concern for organisms developing stress tolerance, as combating pollutant toxicity is usually metabolically costly. Mitochondria, which are responsible for cellular energy production, are a potential target of pollutant toxicity. Thus, understanding mitochondrial energy metabolism will shed light on pollution adaptation. This research examines the oxidative phosphorylation (OxPhos) modulations due to chronic pollution exposure, how gene expression changes covary with OxPhos changes, and genotypic changes potentially underlying these phenotypic changes in response to pollution. Mitochondrial energy metabolism was investigated by quantifying hepatocyte OxPhos function in two independent, polluted F. heteroclitus populations from Elizabeth River, VA and New Bedford Harbor, MA, which are highly contaminated with polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) respectively. Compared to the respective reference populations, altered OxPhos functions were detected in both Elizabeth River and New Bedford Harbor populations, suggesting OxPhos was affected by pollution. Importantly, both polluted populations show elevated respiratory control ratio and ROUTINE respiration, which represent higher ATP production, indicating enhanced, adaptive mitochondrial metabolism in response to chronic pollution.


O2k-Network Lab: US FL Miami Crawford DL


Labels: MiParea: Respiration, nDNA;cell genetics, Comparative MiP;environmental MiP, Pharmacology;toxicology 


Organism: Fishes  Tissue;cell: Liver  Preparation: Permeabilized cells 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2016-11 

Abstract continued

The divergent changes in proton leakiness (LEAK), complex II, and complex IV activity in New Bedford Harbor versus Elizabeth River populations suggest these natural populations’ capacity to develop energy balance for stress tolerance in distinct ways. Acute dosing of a representative PAH and PCB elevated OxPhos uncoupling and inhibited ATP production in reference fish but failed to induce any effects in polluted fish, implying resistance to acute toxicity in polluted populations. Heritability of those OxPhos modulations was examined using laboratory-reared F3 generation fish. Result shows the toxicity resistance and enhanced ROUTINE respiration in Elizabeth River fish are consistent across generations, suggesting genetic adaptation. This is also supported by the lack of OxPhos differences between field-collected and laboratory-reared F3 generation New Bedford fish. To promote the understanding of OxPhos modulations, gene expression was measured on the same fish to identify potential pathways or processes contributing to OxPhos changes. Approximately 3.4% of genes have potentially adaptive gene expression changes in polluted fish, and these genes are enriched for functional clusters for stress responses and regulation of a variety of metabolic processes. Genes that are significantly linked to OxPhos variations are involved in a variety of energy-related metabolic processes and defense responses. These results suggest that pollution has a significant effect on mitochondrial energy metabolism by both directly modulating energy balance and indirectly elevating energy needs due to detoxification. Finally, to identify genetic changes that may underlie the observed phenotypic changes due to chronic pollution exposure, signatures of adaptation were investigated by examining the genetic variation of thousands of markers derived from genotyping-by-sequencing in F. heteroclitus inhabiting the strong pollution cline in New Bedford Harbor, MA. Identified outliers underlying high genetic variation successfully discerned population genetic structure paralleling geographic PCBs. Gene annotation reveals that the pollutantscorrelated outliers are functionally involved in diverse diseases, immune system response, and a variety of metabolic functions (e.g., lipid metabolism and fatty acid biosynthesis), suggesting energy balance is targeted by pollution. Overall, these results suggest that identified outliers are most parsimoniously described as adaptive, and tested functionality of selected outliers supports adaptation. The findings in this thesis contribute to the understanding of how natural populations adapt to pollution from the bioenergetic point of view.