Regulation of the Itaconate Shunt in ME/CFS
Study Aim
This project aims to characterize the mitochondrial function in whole peripheral blood mononuclear cells (PBMCs) in ME/CFS.
Investigators
- Robert Phair, PhD
- Amanda Ooi, PhD
- Ronald Davis, PhD
Updates and Potential
- Our data demonstrates an abnormal mitochondrial function phenotype in ME/CFS cells, in which compromised cells fail to fulfill their own cellular energetic demands due to impaired TCA cycle in their cellular respiration.
- There is also strong evidence for a pathogenic rewiring of mitochondrial central carbon metabolism in ME/CFS cells through the TCA cycle.
STUDY HYPOTHESIS AND DESCRIPTION
We are testing for a modification of mitochondrial central carbon metabolism, known as the itaconate shunt. The itaconate shunt is a 4-step pathway induced by infection or injury and the immune system’s response to that insult. A central tenet of this hypothesis is that ME/CFS is initiated when the itaconate shunt, normally a temporary response of the innate immune system, becomes a chronic impairment of the tricarboxylic acid cycle (TCA) in affected cells.
OBJECTIVES
- To assess and to characterize the mitochondrial function in whole PBMCs derived from healthy controls and ME/CFS patients.
- To test our hypothesis, i.e., the activation of the itaconate shunt and its role in rewiring the mitochondrial substrates from the TCA cycle into the itaconate metabolism pathway in ME/CFS cells.
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