Reduced mitochondrial translation prevents diet-induced metabolic dysfunction but not inflammation

Perks, Kara L.; Ferreira, Nicola; Ermer, Judith A.; Rudler, Danielle L.; Richman, Tara R.; Rossetti, Giulia; Matthews, Vance B.; Ward, Natalie C.; Rackham, Oliver; Filipovska, Aleksandra

doi:10.18632/aging.104010

Cited by 5 publications

(2 citation statements)

References 64 publications

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“…Previous studies showed that PTCD1 is straightly linked to and exhausted leucine mitochondrial tRNAs, restraining the translation of mitochondrial-encoded proteins and inhibiting oxidative phosphorylation in the mitochondria [17,23]. Its abnormal expression may lead to many diseases, such as metabolic dysfunction, obesity, and neoplasms [14,21,[24][25][26]. However, the implication of its expression in prognosis and diagnosis of patients with BLCA remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Zhou

et al. 2022

Journal of Oncology

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Pentatricopeptide repeat domain 1 (PTCD1) was reported to regulate mitochondrial metabolism and oxidative phosphorylation. However, the effect and mechanism of PTCD1 in the development of bladder urothelial carcinoma (BLCA) remain unclear. The databases from The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) were used to analyze the expression changes, clinical features, and prognostic values of PTCD1. A nomogram was built to predict the prognostic outcomes of BLCA cases. The potential genes interacting with PTCD1 were explored by Weighted Gene Coexpression Network Analysis (WGCNA). The estimation of associations between PTCD1 and tumor mutations, tumor immunities, and m6A methylations was performed. The study found that the gradual decrease of PTCD1 expression was observed with the increase of stage and grade. Low PTCD1 expression was greatly correlated with higher pathological stage, N stage, and poor prognosis in TCGA cohorts; interestingly, low-grade BLCA cases all exhibited high expression of PTCD1. HPA database analysis implied that the expression of PTCD1 protein in BLCA was lower than that in normal bladder tissue, and the protein expression of PTCD1 in high-grade BLCA was lower than that in low-grade BLCA. Multivariate Cox regression analysis indicated that PTCD1 may serve as an independent factor influencing prognosis of BLCA. Mechanistically, PTCD1 played a regulatory role in BLCA progression through multiple tumor-related pathways containing PI3K-Akt signaling, ECM-receptor interaction, oxidative phosphorylation, and extracellular matrix organization. WGCNA reported that PTCD1 had a strong positive correlation with POLR2J, ZNHT1, ATP5MF, PDAP1, BUD31, and COPS6. Besides, the mRNA expression of PTCD1 was negatively associated with immune cells’ infiltrations, immune functions, and checkpoints, especially with some m6A methylation regulators in BLCA. In sum, downregulation of PTCD1 expression may be involved in the development of BLCA and remarkably correlated with poor prognosis. Meantime, it showed an influence in immune cell infiltration and may serve as an agreeable prognostic indicator in BLCA.

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Section: Discussionmentioning

confidence: 99%

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Zhou

et al. 2022

Journal of Oncology

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“…For terminal insulin testing, 20-week-old mice were injected with insulin (1 U/kg) and euthanized by cervical dislocation 5 min after the injection, followed by tissue collection (snap freezing). SCFA profiling was performed as described previously ( 48 ) to measure the concentration of acetate, butyrate, and propionate as nanomoles per microliter of serum. Serum was analyzed by Pathwest Laboratory Medicine (Nedlands, WA, Australia) for levels of albumin, ALT, cholesterol, TAG, LDL, HDL, and potassium (K + ).…”

Section: Methodsmentioning

confidence: 99%

A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

et al. 2021

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Mitochondrial energy metabolism plays an important role in the pathophysiology of insulin resistance. Recently, a missense N437S variant was identified in the MRPP3 gene, which encodes a mitochondrial RNA processing enzyme within the RNase P complex, with predicted impact on metabolism. We used CRISPR-Cas9 genome editing to introduce this variant into the mouse Mrpp3 gene and show that the variant causes insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet  cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis in the Mrpp3 variant mice on a high-fat diet. Our findings reveal that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population.

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Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation

So,

Wu,

Tai

et al. 2024

Atherosclerosis

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Reduced mitochondrial translation prevents diet-induced metabolic dysfunction but not inflammation

Cited by 5 publications

References 64 publications

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

Downregulation of PTCD1 in Bladder Urothelial Carcinoma Predicts Poor Prognosis and Levels of Immune Infiltration

A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation

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