Publication details
The effect of glutamine starvation on the metabolism, oxidative stress, and content of mitochondrial RNAs in cancer-derived EVs
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| Year of publication | 2024 |
| Type | Appeared in Conference without Proceedings |
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| Citation | |
| Description | Induction of autophagy is a survival mechanism for starved or stressed cancer cells, altering signalling and causing reorganisation in the tumour microenvironment. This study examined the metabolic and signalling impacts of glutamine (Gln) starvation-induced and NVPBEZ235- induced autophagy in cancer cells. Both treatments decreased ATP production from glycolysis and oxidative phosphorylation, underscoring the role of active mTOR in glycolysis. While both treatments reduced ATP production, only Gln starvation caused oxidative damage, lipid peroxidation, and mitochondrial fragmentation. This oxidative stress was linked to decreased levels of GPX4, an antioxidant defence protein. Gln starvation also increased mitochondrial RNA levels in EVs, indicating a mechanism for removing damaged mitochondrial components. The mitophagy-related protein BNIP3 increased with BEZ treatment but not with Gln starvation, suggesting limited removal of damaged mitochondria under Gln starvation. Gln starvation and BEZ altered the EV-associated cytokine secretome, with both treatments increasing inflammatory cytokines like IL-6, IL-13, and CCL5, which promote tumour progression and immune cell recruitment. Interestingly, Gln starvation reduced IL-8, GRO-?, and IL-2 levels while increasing oxidative stress. Further, Gln starvation decreased EV production without changing their characteristic molecules. RNA profiling of EVs from FaDu cells showed an abundance of protein-coding RNAs and some ribosomal RNA after Gln starvation. The study found that Gln starvation increases mitochondrial RNAs in EVs from HNSCC cells, reflecting cellular metabolic reprogramming. Although mitochondrial RNA levels in EVs from HNSCC patients and healthy controls showed no significant difference, the findings highlight distinct autophagy inducer's metabolic and signalling effects on cancer cells and their EVs. |