The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat

Found in all organisms, pyruvate dehydrogenase complexes (PDC) are the keystones of prokaryotic and eukaryotic energy metabolism. In eukaryotic organisms these multi-component megacomplexes provide a crucial mechanistic link between cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TC...

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Bibliographic Details
Published in:Mitochondrion 2023-05, Vol.70, p.59-102
Main Authors: Stacpoole, Peter W., McCall, Charles E.
Format: Article
Language:English
Subjects:
Aerobic glycolysis
Aging
Animals
Cancer
Citric Acid Cycle - physiology
Diabetes
Embryogenesis
Energy Metabolism
Glycolysis
Inflammation
Neurodegeneration
Oxidative Phosphorylation
Pyruvate dehydrogenase complex
Pyruvate Dehydrogenase Complex - chemistry
Pyruvate Dehydrogenase Complex - metabolism
Sepsis
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Summary:Found in all organisms, pyruvate dehydrogenase complexes (PDC) are the keystones of prokaryotic and eukaryotic energy metabolism. In eukaryotic organisms these multi-component megacomplexes provide a crucial mechanistic link between cytoplasmic glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle. As a consequence, PDCs also influence the metabolism of branched chain amino acids, lipids and, ultimately, oxidative phosphorylation (OXPHOS). PDC activity is an essential determinant of the metabolic and bioenergetic flexibility of metazoan organisms in adapting to changes in development, nutrient availability and various stresses that challenge maintenance of homeostasis. This canonical role of the PDC has been extensively probed over the past decades by multidisciplinary investigations into its causal association with diverse physiological and pathological conditions, the latter making the PDC an increasingly viable therapeutic target. Here we review the biology of the remarkable PDC and its emerging importance in the pathobiology and treatment of diverse congenital and acquired disorders of metabolic integration.
ISSN:1567-7249
1872-8278
DOI:10.1016/j.mito.2023.02.007