Metabolic Reprogramming in Response to Mitochondrial Electron Transport Chain Dysfunction

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August 2021

Authors

Lesner, Nicholas Paul

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Abstract

Mitochondrial electron transport chain (ETC) diseases are genetic disorders of energy production with an occurrence rate of approximately 1:4300 and no effective treatment options. Here we show in vitro models of mitochondrial ETC dysfunction display shunting of major carbon sources (glucose and glutamine) from the TCA cycle. Additionally, SLC7A11 (a plasma membrane glutamate/cystine antiporter) promotes pyruvate oxidation in the mitochondria via generation of an electron acceptor, a-ketobutyrate. Furthermore, in the liver, loss of ETC complex I results in no observable clinical or biochemical phenotype, while complex IV deficiency results in steatosis, liver damage, and significant biochemical alterations. The studies herein demonstrate metabolic reprogramming is important in mitochondrial dysfunction; however, the reprogramming is ETC complex and tissue specific.

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