Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma.

ABSTRACT: Metabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation, and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial pathways has remained unexplored. Here, we investigate metabolic consequences of uniporter loss- and gain-of-function using uniporter knockout cells and the liver cancer fibrolamellar carcinoma (FLC), which we demonstrate to have elevated mitochondrial calcium levels. Our results reveal that branched-chain amino acid (BCAA) catabolism and the urea cycle are uniporter-regulated metabolic pathways. Reduced uniporter function boosts

SUBMITTER: Marsh NM 

PROVIDER: S-EPMC11160645 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature