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Published on: January 22, 2017
Poliovirus induces an early impairment of mitochondrial function by inhibiting succinate dehydrogenase activity
A Koundouris1, G E Kass, C R Johnson
1School of Biological Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
Abstract:
Poliovirus infection of COS-1 and T47D cells caused a rapid decrease in total cell respiration, and this was attributed to an inhibition of mitochondrial respiration. The stimulation of mitochondrial respiration by pyruvate plus malate or succinate was impaired in saponin-permeabilised cells. However, this inhibition could be overcome by the addition of N,N,N',N'-tetramethyl-1, 4-phenylenediamine and ascorbate. The activity of succinate dehydrogenase was impaired in parallel with the inhibition of mitochondrial respiration during poliovirus infection. This shows that mitochondrial function is profoundly altered during poliovirus infection and that this occurs primarily through inhibition of electron flow at complex II of the mitochondrial respiratory chain.
Insights
Poliovirus infection significantly impairs cellular respiration by inhibiting mitochondrial function. This viral effect primarily targets electron flow at Complex II, impacting cellular energy production.
Area of Science:
- Virology
- Cell Biology
- Mitochondrial Respiration
Background:
- Poliovirus infection is known to affect host cell metabolism.
- Mitochondrial respiration is crucial for cellular energy production.
Purpose of the Study:
- To investigate the impact of poliovirus infection on cellular and mitochondrial respiration.
- To identify the specific mechanisms by which poliovirus affects mitochondrial function.
Main Methods:
- Assessing total cell respiration in infected COS-1 and T47D cells.
- Measuring mitochondrial respiration in saponin-permeabilized cells using various substrates.
- Evaluating the activity of succinate dehydrogenase.
Main Results:
- Poliovirus infection led to a significant decrease in total cell respiration.
- Mitochondrial respiration, when stimulated by pyruvate/malate or succinate, was impaired.
- The inhibition of mitochondrial respiration could be overcome by specific electron donors (N,N,N',N'-tetramethyl-1,4-phenylenediamine and ascorbate).
- Succinate dehydrogenase activity was reduced concurrently with the inhibition of mitochondrial respiration.
Conclusions:
- Poliovirus profoundly alters mitochondrial function in infected cells.
- The primary mechanism involves the inhibition of electron flow at Complex II of the mitochondrial respiratory chain.
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