Mitochondrial ribosomal protein genes connected with Alzheimer’s and tellurite toxicity

Giudice, Luigi Del; Alifano, Pietro; Calcagnile, Matteo; Schiavi, Elia Di; Bertapelle, Carla; Aletta, Mariarosaria; Pontieri, Paola

doi:10.1016/j.mito.2022.02.006

Cited by 10 publications

(16 citation statements)

References 174 publications

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“…MRPS7, MSPS5, MRPS23, MRPL15, MRPL21, and MRPL17 are members of mitochondrial ribosomal genes, encoding subunits of mitochondrial ribosome proteins (MRPs), which can help in protein synthesis inside mitochondria [ 35 ]. This implies that mitochondria may play a critical role in cuproptosis.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas

Tang

Zhao

et al. 2022

Cancers

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Head and neck squamous carcinoma (HNSC) is a frequent and deadly malignancy that is challenging to manage. The existing treatment options have considerable efficacy limitations. Hence, the identification of new therapeutic targets and the development of efficacious treatments are urgent needs. Cuproptosis, a non-apoptotic programmed cell death caused by excess copper, has only very recently been discovered. The present study investigated the prognostic importance of genes involved in cuproptosis through the mRNA expression data and related clinical information of HNSC patients downloaded from public databases. Our results revealed that many cuproptosis-related genes were differentially expressed between normal and HNSC tissues in the TCGA cohort. Moreover, 39 differentially expressed genes were associated with the prognosis of HNSC patients. Then, a 24-gene signature was identified in the TCGA cohort utilizing the LASSO Cox regression model. HNSC expression data used for validation were obtained from the GEO database. Consequently, we divided patients into high- and low-risk groups based on the 24-gene signature. Furthermore, we demonstrated that the high-risk group had a worse prognosis when compared to the low-risk group. Additionally, significant differences were found between the two groups in metabolic pathways, immune microenvironment, etc. In conclusion, we found a cuproptosis-related gene signature that can be used effectively to predict OS in HNSC patients. Thus, targeting cuproptosis might be an alternative and promising strategy for HNSC patients.

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Section: Resultsmentioning

confidence: 99%

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas

Tang

Zhao

et al. 2022

Cancers

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“…Mitochondrial RNA metabolism falls into diverse functions of mitochondrial complexes, tRNA, and rRNA. Although the roles of mitochondrial RNA in AD remain unclear, mitochondrial dysfunctions and cascades have been involved in AD pathogenesis, thus providing potential markers for neurodegeneration [ 21 , 22 , 23 , 24 ]. The mitochondrial coding and non-coding RNA are increased in the circulating extracellular vesicles in AD and mild cognitive impairment (MCI) [ 25 , 26 ]; the AD genes in the category of this study include MT-ND1-4,6, MT-ND4L, MT-ATP6, MT-ATP8, MT-CYB (or MT-CYBT), MT-CO1, and MT-RNR1 ( Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

Genetic Networks of Alzheimer’s Disease, Aging, and Longevity in Humans

Balmorez

Sakazaki

Murakami

2023

IJMS

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Human genomic analysis and genome-wide association studies (GWAS) have identified genes that are risk factors for early and late-onset Alzheimer’s disease (AD genes). Although the genetics of aging and longevity have been extensively studied, previous studies have focused on a specific set of genes that have been shown to contribute to or are a risk factor for AD. Thus, the connections among the genes involved in AD, aging, and longevity are not well understood. Here, we identified the genetic interaction networks (referred to as pathways) of aging and longevity within the context of AD by using a gene set enrichment analysis by Reactome that cross-references more than 100 bioinformatic databases to allow interpretation of the biological functions of gene sets through a wide variety of gene networks. We validated the pathways with a threshold of p-value < 1.00 × 10−5 using the databases to extract lists of 356 AD genes, 307 aging-related (AR) genes, and 357 longevity genes. There was a broad range of biological pathways involved in AR and longevity genes shared with AD genes. AR genes identified 261 pathways within the threshold of p < 1.00 × 10−5, of which 26 pathways (10% of AR gene pathways) were further identified by overlapping genes among AD and AR genes. The overlapped pathways included gene expression (p = 4.05 × 10−11) including ApoE, SOD2, TP53, and TGFB1 (p = 2.84 × 10−10); protein metabolism and SUMOylation, including E3 ligases and target proteins (p = 1.08 × 10−7); ERBB4 signal transduction (p = 2.69 × 10−6); the immune system, including IL-3 and IL-13 (p = 3.83 × 10−6); programmed cell death (p = 4.36 × 10−6); and platelet degranulation (p = 8.16 × 10−6), among others. Longevity genes identified 49 pathways within the threshold, of which 12 pathways (24% of longevity gene pathways) were further identified by overlapping genes among AD and longevity genes. They include the immune system, including IL-3 and IL-13 (p = 7.64 × 10−8), plasma lipoprotein assembly, remodeling and clearance (p < 4.02 × 10−6), and the metabolism of fat-soluble vitamins (p = 1.96 × 10−5). Thus, this study provides shared genetic hallmarks of aging, longevity, and AD backed up by statistical significance. We discuss the significant genes involved in these pathways, including TP53, FOXO, SUMOylation, IL4, IL6, APOE, and CEPT, and suggest that mapping the gene network pathways provide a useful basis for further medical research on AD and healthy aging.

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“…CRGs including SLC25A5, SLC23A2, PDHX, and COX7B, all of which can impede mitochondrial energy metabolism, have been reported to be correlated with prognosis of ESCA patients [ 42 , 57 ]. MRPS7, a ribosomal protein, is involved in protein synthesis in mitochondria [ 58 ]. MRPS7 expression is higher in HNSC patients [ 59 ] (Table 1 ).…”

Section: Cuproptosis In Cancersmentioning

confidence: 99%

Role of cuproptosis in understanding diseases

Cao,

Wang,

Sun

et al. 2023

Human Cell

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Cell death is involved in a wide range of physiological and pathological processes. Recently, the term “cuproptosis” was coined to describe a novel type of cell death. This type of cell death, characterized by copper accumulation and proteotoxic stress, is a copper-dependent manner of death. Despite the progress achieved toward a better understanding of cuproptosis, mechanisms and related signaling pathways in physiology and pathology across various diseases remain to be proved. This mini review summarizes current research on cuproptosis and diseases, providing insights into prospective clinical therapies via targeting cuproptosis.

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Mitochondrial ribosomal protein genes connected with Alzheimer’s and tellurite toxicity

Cited by 10 publications

References 174 publications

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas

Identification of a Novel Cuproptosis-Related Gene Signature for Prognostic Implication in Head and Neck Squamous Carcinomas

Genetic Networks of Alzheimer’s Disease, Aging, and Longevity in Humans

Role of cuproptosis in understanding diseases

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