Glutamine metabolism in diseases associated with mitochondrial dysfunction

Bornstein, Rebecca; Mulholland, Michael W.; Sedensky, Margaret M.; Morgan, Phil G.; Johnson, Simon C.

doi:10.1016/j.mcn.2023.103887

Cited by 13 publications

(1 citation statement)

References 163 publications

(208 reference statements)

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“…In addition to glycolysis, mitochondrial glutamine metabolism is the most common energy source for cancer cells. Glutamine is a nonessential amino acid (NEAA) that enters the cell via the amino acid transporters, such as ASCT2/SLC1A5, and is then catalyzed to glutamate by glutaminase in the mitochondria, and mitochondrial glutamate is subsequently converted into α‐ketoglutarate (α‐KG), which can help rapidly proliferating cancer cells meet the increasing demand for ATP and biosynthetic precursors and reducing agents [ 8 , 9 ]. The survival and proliferation of proliferating cancer cells rely largely on glutamine metabolism [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression

Hou,

Chen,

Wang

2024

Clinical Respiratory J

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BackgroundMitochondrial ribosomal protein L35 (MRPL35) has been reported to contribute to the growth of non–small cell lung cancer (NSCLC) cells. However, the functions and mechanisms of MRPL35 on glutamine metabolism in NSCLC remain unclear.MethodsThe detection of mRNA and protein of MRPL35, ubiquitin‐specific protease 39 (USP39), and solute carrier family 7 member 5 (SLC7A5) was conducted using qRT‐PCR and western blotting. Cell proliferation, apoptosis, and invasion were evaluated using the MTT assay, EdU assay, flow cytometry, and transwell assay, respectively. Glutamine metabolism was analyzed by detecting glutamine consumption, α‐ketoglutarate level, and glutamate production. Cellular ubiquitination analyzed the deubiquitination effect of USP39 on MRPL35. An animal experiment was conducted for in vivo analysis.ResultsMRPL35 was highly expressed in NSCLC tissues and cell lines, and high MRPL35 expression predicted poor outcome in NSCLC patients. In vitro analyses suggested that MRPL35 knockdown suppressed NSCLC cell proliferation, invasion, and glutamine metabolism. Moreover, MRPL35 silencing hindered tumor growth in vivo. Mechanistically, USP39 stabilized MRPL35 expression by deubiquitination and then promoted NSCLC cell proliferation, invasion, and glutamine metabolism. In addition, MRPL35 positively affected SLC7A5 expression in NSCLC cells in vitro and in vivo. Moreover, the anticancer effects of MRPL35 silencing could be rescued by SLC7A5 overexpression in NSCLC cells.ConclusionMRPL35 expression was stabilized by USP39‐induced deubiquitination in NSCLC cells, and knockdown of MRPL35 suppressed NSCLC cell proliferation, invasion, and glutamine metabolism in vitro and impeded tumor growth in vivo by upregulating SLC7A5, providing a promising therapeutic target for NSCLC.

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Section: Introductionmentioning

confidence: 99%

MRPL35 Induces Proliferation, Invasion, and Glutamine Metabolism in NSCLC Cells by Upregulating SLC7A5 Expression

Hou,

Chen,

Wang

2024

Clinical Respiratory J

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Targeting Mitochondria: Influence of Metabolites on Mitochondrial Heterogeneity

Joof,

Ren,

Zhou

et al. 2024

Cell Biochemistry & Function

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Mitochondria are vital organelles that provide energy for the metabolic processes of cells. These include regulating cellular metabolism, autophagy, apoptosis, calcium ions, and signaling processes. Despite their varying functions, mitochondria are considered semi‐independent organelles that possess their own genome, known as mtDNA, which encodes 13 proteins crucial for oxidative phosphorylation. However, their diversity reflects an organism's adaptation to physiological conditions and plays a complex function in cellular metabolism. Mitochondrial heterogeneity exists at the single‐cell and tissue levels, impacting cell shape, size, membrane potential, and function. This heterogeneity can contribute to the progression of diseases such as neurodegenerative diseases, metabolic diseases, and cancer. Mitochondrial dynamics enhance the stability of cells and sufficient energy requirement, but these activities are not universal and can lead to uneven mitochondria, resulting in heterogeneity. Factors such as genetics, environmental compounds, and signaling pathways are found to affect these cellular processes and heterogeneity. Additionally, the varying roles of metabolites such as NADH and ATP affect glycolysis's speed and efficiency. An imbalance in metabolites can impair ATP production and redox potential in the mitochondria. Therefore, this review will explore the influence of metabolites in shaping mitochondrial morphology, how these changes contribute to age‐related diseases and the therapeutic targets for regulating mitochondrial heterogeneity.

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