Light shed on a non-canonical TCA cycle: cell state regulation beyond mitochondrial energy production

Abstract

In this recent study,1 the authors analyzed the metabolic gene essentiality scores from genome-wide loss of function CRISPR screens in 769 human cancer cell lines and noticed that TCA cycle-associated genes clustered in two separate groups: one forming the traditional TCA cycle and another related to a non-canonical TCA cycle module. They monitored both modules with elegant tracing studies using [U-13C]glucose which generates citrate labeled with two 13C atoms (M+2).

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