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NFκB and JNK pathways mediate metabolic adaptation upon ESCRT-I deficiency.
Cell. Mol. Life Sci. 81:458 (2024)
Endosomal Sorting Complexes Required for Transport (ESCRTs) are crucial for delivering membrane receptors or intracellular organelles for lysosomal degradation which provides the cell with lysosome-derived nutrients. Yet, how ESCRT dysfunction affects cell metabolism remained elusive. To address this, we analyzed transcriptomes of cells lacking TSG101 or VPS28 proteins, components of ESCRT-I subcomplex. ESCRT-I deficiency reduced the expression of genes encoding enzymes involved in oxidation of fatty acids and amino acids, such as branched-chain amino acids, and increased the expression of genes encoding glycolytic enzymes. The changes in metabolic gene expression were associated with Warburg effect-like metabolic reprogramming that included intracellular accumulation of lipids, increased glucose/glutamine consumption and lactate production. Moreover, depletion of ESCRT-I components led to expansion of the ER and accumulation of small mitochondria, most of which retained proper potential and performed ATP-linked respiration. Mechanistically, the observed transcriptional reprogramming towards glycolysis in the absence of ESCRT-I occurred due to activation of the canonical NFκB and JNK signaling pathways and at least in part by perturbed lysosomal degradation. We propose that by activating the stress signaling pathways ESCRT-I deficiency leads to preferential usage of extracellular nutrients, like glucose and glutamine, for energy production instead of lysosome-derived nutrients, such as fatty acids and branched-chain amino acids.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Escrt ; Jnk ; Nfκb ; Fatty Acid Oxidation ; Glycolysis ; Mitochondria; Fatty-acid; Down-regulation; Nile-red; Receptor; Activation; Glycolysis; Glucose; Interleukin-8; Endocytosis; Physiology
ISSN (print) / ISBN
1420-682X
e-ISSN
1420-9071
Quellenangaben
Volume: 81,
Issue: 1,
Article Number: 458
Publisher
Birkhäuser
Publishing Place
Picassoplatz 4, Basel, 4052, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
Fundacja na rzecz Nauki Polskiej