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Updated: May 30, 2026
08:57
Simultaneous Measurement of Superoxide/Hydrogen Peroxide and NADH Production by Flavin-containing Mitochondrial Dehydrogenases
Published on: February 24, 2018
Increased superoxide accumulation in pyruvate dehydrogenase complex deficient fibroblasts
Lyudmyla G Glushakova1, Sharon Judge, Alex Cruz
1Department of Medicine (Division of Endocrinology and Metabolism), College of Medicine, University of Florida, Gainesville, FL 32611, USA.
Molecular Genetics and Metabolism
|August 18, 2011
Summary
Pyruvate dehydrogenase complex (PDC) deficiency causes cellular energy failure and lactic acidosis by increasing harmful superoxide radicals. This impairs the cell's ability to remove these radicals, worsening the condition.
Area of Science:
- Biochemistry
- Cell Biology
- Metabolic Disorders
Background:
- Pyruvate dehydrogenase complex (PDC) is vital for cellular energy homeostasis.
- PDC loss-of-function mutations cause congenital lactic acidosis and energy failure.
- Biochemical consequences of PDC deficiency are not fully understood.
Purpose of the Study:
- To investigate the biochemical consequences of PDC deficiency.
- To determine if altered PDC flux causes oxidative stress.
- To explore the role of hypoxia-inducible factor 1 alpha (HIF1α) in PDC deficiency.
Main Methods:
- Primary skin fibroblast cultures from PDC-deficient patients and healthy controls.
- Assessed cell growth, viability, superoxide levels, and enzyme activities.
- Measured expression of manganese superoxide dismutase, uncoupling protein 2, and HIF1α.
Main Results:
- PDC-deficient fibroblasts showed reduced growth and viability.
- Accumulation of superoxide (O(2)(.-)) at complex III was observed.
- Decreased manganese superoxide dismutase activity and uncoupling protein 2 expression.
- Increased HIF1α expression in patient cells.
Conclusions:
- PDC deficiency leads to increased superoxide accumulation and impaired removal.
- Increased HIF1α expression may drive glycolysis and lactate production.
- HIF1α may further suppress PDC activity via pyruvate dehydrogenase kinase.
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