Phylogenetic relationships of the Mangrove Hummingbird, "Amazilia" boucardi (Apodiformes: Trochilidae) of Costa Rica / Relaciones filogenéticas del Colibrí manglero "Amazilia" boucardi (Apodiformes: Trochilidae) de Costa Rica

Abstract Introduction: A recent revision of the generic classification of the Trochilidae based on DNA sequences revealed many inconsistencies with the current generic classification, largely based on plumage characters subject to homoplasy, especially in the Trochilini, the largest tribe. A thorough generic reorganization brought the classification into accord with the phylogeny, but due to lack of genetic data, two species remained unclassified. One of these was the Mangrove Hummingbird, "Amazilia" boucardi, endemic to Costa Rica and included in the IUCN red list of threatened species. Objective: To obtain molecular evidence to clarify the generic relationships of "A." boucardi. Methods: We isolated DNA from tissues of this species and amplified 4 nuclear and 4 mitochondrial fragments and compared these with homologous fragments from 56 species in the Trochilini, constructing phylogenetic trees with maximum likelihood and Bayesian methods. Results: Our phylogenetic analyses confirmed the placement of boucardi in the Trochilini and definitely excluded it from Amazilia but placed it with high confidence in the genus Chrysuronia Bonaparte, 1850, within which its closest relative is C. coeruleogularis, which also inhabits mangroves. Conclusions: Our genetic data based on nuclear and mitochondrial regions clearly indicate the relationship of A. boucardi and L. coeruleogularis. Moreover, it is also supported by their habitat distribution in the mangroves of the Pacific coast of Costa Rica and Western Panama. Therefore, we suggested to exclude A. boucardi as "incertae sedis".

Resumen Introducción: Una revisión reciente de la clasificación de la familia Trochilidae con base en secuencias de ADN demostró muchas incongruencias con la clasificación genérica previa, que había sido hecho con base en caracteres del plumaje muy sujetos a homoplasia, especialmente en la tribu más grande, Trochillini. Una reorganización de los géneros logró llevar su clasificación genérica a la concordancia con la filogenia, pero debido a la ausencia de datos genéticos, dos especies permanecieron sin clasificar. Una de estas fue el colibrí de manglar Amazilia boucardi, una especie endémica de Costa Rica, considerada como amenazada en la lista roja de la UICN. Objetivo: Obtener evidencia molecular para esclarecer las relaciones genéricas de A. boucardi. Métodos: Se aisló ADN de tejidos de esta especie y se amplificaron 4 fragmentos de ADN del núcleo y 5 de la mitocondria, y se compararon con fragmentos homólogos de 56 especies en la tribu Trochillini, generando árboles filogenéticos con métodos de máxima verosimilitud y bayesiano. Resultados: Los análisis filogénticos obtenidos confirmaron la ubicación de boucardi en Trochilini y definitivamente la excluyó del género Amazilia, pero la ubicó con un alto grado de confianza en el género Chrysuronia Bonaparte, 1850, dentro los cuales su pariente más cercano es C. coeruleogularis, que también habita manglares. Conclusiones: Nuestros datos genéticos basados en regiones nucleares y mitocondriales indican claramente la relación entre A. boucardi and L. coeruleogularis. Es más, lo anterior se sustenta por su distribución en los manglares de la costa Pacífica de Costa Rica y oeste de Panamá. Por lo tanto, sugerimos excluir a A. boucardi como "incertae sedis".

Purifying selection drove the adaptation of mitochondrial genes along with correlation of gene rearrangements and evolutionary rates in two subfamilies of Whitefly (Insecta: Hemiptera).

Insect mitochondrial genomes (mitogenomes) are usually represented by a conserved gene order. Whiteflies exhibit gene rearrangement in their mitogenomes; however, understanding how nucleotide substitution rates shape gene rearrangement in whiteflies is unclear due to the limited number of mitogenomes. Additionally, the mechanisms by which selection pressure drives adaptations in mitochondrial genes in the two subfamilies of whiteflies are not yet known. Here, we analyzed 18 whitefly mitogenomes, including one newly generated mitogenome, to compare nucleotide substitution rates, selection pressure, and gene arrangements. The newly generated mitogenome is reported along with reannotation of Pealius mori and comparisons to other whitefly mitogenomes. Comparative studies on nucleotide composition of 18 whiteflies revealed the positive GC skewness, confirming the reversal of strand asymmetry. We found 11 rearranged gene orders within two subfamilies of whiteflies with 8-18 breakpoints of gene rearrangements. Members of the subfamily Aleyrodinae exhibit more complex pathways in the evolution of gene order as compared to the subfamily Aleurodicinae. Our findings also revealed that the increase or reduction of nucleotide substitution rates does not have an impact on any of the gene rearrangement scenarios depicting neutral correlation. Selection pressure analysis revealed that the mitogenomes from members of both the subfamilies Aleurodicinae and Aleyrodinae are characterized by intense purifying selection pressure.

Exploring necrosis-associated mitochondrial gene signatures: revealing their role in prognosis and immunotherapy of renal clear cell carcinoma.

Mitochondrial dysfunction and necrotic apoptosis, pivotal in therapeutic strategies for multiple diseases, lack comprehensive understanding in the context of renal clear cell carcinoma (ccRCC). This study explores their potential as valuable tools for ccRCC prediction, prevention, and personalized medical care. Transcriptomic and clinical datasets were acquired from the Cancer Genome Atlas (TCGA) repository. Mitochondrial and necrosis-associated gene sets were sourced from MitoCarta3.0 and the KEGG Pathway databases, respectively. Six necrosis-related mitochondrial genes (nc-MTGs) with prognostic significance were analyzed and screened, and a prognostic model was constructed. The accuracy of the model was verified using external data (E-MTAB-1980). TISCH was used to explore nc-MTGs at the cellular level. Finally, the expression level of BH3 interacting domain death agonist (BID) in ccRCC cell line was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the effect of BID down-regulation on tumor cell migration was verified by transwell assays and wound-healing experiments. We established and validated a prognostic model for clear cell renal cell carcinoma (ccRCC) utilizing six necrosis-related mitochondrial genes (nc-MTGs), affirming its efficacy in evaluating tumor progression. RT-PCR results showed that BID expression was up-regulated in ccRCC tissues compared with controls and exhibited oncogenic effects. In vitro cell function experiments showed that BID may be an important factor affecting the migration of ccRCC. Our study is the first to elucidate the biological functions and prognostic significance of mitochondrial molecules related to necroptosis, providing a new way to evaluate mitochondrial therapeutics in patients with ccRCC.

Identification and experimental validation of KMO as a critical immune-associated mitochondrial gene in unstable atherosclerotic plaque.

BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.

Protein truncating variants in mitochondrial-related nuclear genes and the risk of chronic liver disease.

BACKGROUND: Mitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored. METHODS: We extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality. RESULTS: 96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e - 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15-6.85), 2.82-fold (1.69-4.72), and 4.41-fold (3.04-6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome. CONCLUSIONS: Our findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.

Rice floury endosperm26 encoding a mitochondrial single-stranded DNA-binding protein is essential for RNA-splicing of mitochondrial genes and endosperm development.

Endosperm, the major storage organ in cereal grains, determines the grain yield and quality. Mitochondria provide the energy for dry matter accumulation, in the endosperm development. Although mitochondrial single-stranded DNA-binding proteins (mtSSBs) play a canonical role in the maintenance of single-stranded mitochondrial DNA, their molecular functions in RNA processing and endosperm development remain obscure. Here, we report a defective rice endosperm mutant, floury endosperm26 (flo26), which develops abnormal starch grains in the endosperm. Map-based cloning and complementation experiments showed that FLO26 allele encodes a mitochondrial single-stranded DNA-binding protein, named as mtSSB1.1. Loss of function of mtSSB1.1 affects the transcriptional level of many mitochondrially-encoded genes and RNA splicing of nad1, a core component of respiratory chain complex I in mitochondria. As a result, dysfunctional mature nad1 led to dramatically decreased complex I activity, thereby reducing ATP production. Our results reveal that mtSSB1.1 plays an important role in the maintenance of mitochondrial function and endosperm development by stabilizing the splicing of mitochondrial RNA in rice.

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Genetic diversity and population structure of Physella acuta (Gastropoda: Physidae) in Thailand using mitochondrial gene markers: COI and 16S rDNA.

Physella acuta is a freshwater snail native to North America. Understanding the phylogeography and genetic structure of P. acuta will help elucidate its evolution. In this study, we used mitochondrial (COI and 16S rDNA) and nuclear (ITS1) markers to identify the species and examine its genetic diversity, population structure, and demographic history of P. acuta in Thailand. Phylogenetic and network analyses of P. acuta in Thailand pertained to clade A, which exhibits a global distribution. Analysis of the genetic structure of the population revealed that the majority of pairwise comparisons showed no genetic dissimilarity. An isolation-by-distance test indicates no significant correlation between genetic and geographical distances among P. acuta populations, suggesting that gene flow is not restricted by distance. Demographic history and haplotype network analyses suggest a population expansion of P. acuta, as evidenced by the star-like structure detected in the median-joining network. Based on these results, we concluded that P. acuta in Thailand showed gene flow and recent population expansion. Our findings provide fundamental insights into the genetic variation of P. acuta in Thailand.

Effect of locomotor preference on the evolution of mitochondrial genes in Bovidae.

Locomotor preferences and habitat types may drive animal evolution. In this study, we speculated that locomotor preference and habitat type may have diverse influences on Bovidae mitochondrial genes. We used selection pressure and statistical analysis to explore the evolution of mitochondrial DNA (mtDNA) protein-coding genes (PCGs) from diverse locomotor preferences and habitat types. Our study demonstrates that locomotor preference (energy demand) drives the evolution of Bovidae in mtDNA PCGs. The habitat types had no significant effect on the rate of evolution in Bovidae mitochondrial genes. Our study provides deep insight into the adaptation of Bovidae.

Machine learning-based algorithm identifies key mitochondria-related genes in non-alcoholic steatohepatitis.

BACKGROUND: Evidence suggests that hepatocyte mitochondrial dysfunction leads to abnormal lipid metabolism, redox imbalance, and programmed cell death, driving the onset and progression of non-alcoholic steatohepatitis (NASH). Identifying hub mitochondrial genes linked to NASH may unveil potential therapeutic targets. METHODS: Mitochondrial hub genes implicated in NASH were identified via analysis using 134 algorithms. RESULTS: The Random Forest algorithm (RF), the most effective among the 134 algorithms, identified three genes: Aldo-keto reductase family 1 member B10 (AKR1B10), thymidylate synthase (TYMS), and triggering receptor expressed in myeloid cell 2 (TREM2). They were upregulated and positively associated with genes promoting inflammation, genes involved in lipid synthesis, fibrosis, and nonalcoholic steatohepatitis activity scores in patients with NASH. Moreover, using these three genes, patients with NASH were accurately categorized into cluster 1, exhibiting heightened disease severity, and cluster 2, distinguished by milder disease activity. CONCLUSION: These three genes are pivotal mitochondrial genes implicated in NASH progression.

Identification of sepsis-associated mitochondrial genes through RNA and single-cell sequencing approaches.

BACKGROUND: Sepsis ranks among the most formidable clinical challenges, characterized by exorbitant treatment costs and substantial demands on healthcare resources. Mitochondrial dysfunction emerges as a pivotal risk factor in the pathogenesis of sepsis, underscoring the imperative to identify mitochondrial-related biomarkers. Such biomarkers are crucial for enhancing the accuracy of sepsis diagnostics and prognostication. METHODS: In this study, adhering to the SEPSIS 3.0 criteria, we collected peripheral blood within 24 h of admission from 20 sepsis patients at the ICU of the Southwest Medical University Affiliated Hospital and 10 healthy volunteers as a control group for RNA-seq. The RNA-seq data were utilized to identify differentially expressed RNAs. Concurrently, mitochondrial-associated genes (MiAGs) were retrieved from the MitoCarta3.0 database. The differentially expressed genes were intersected with MiAGs. The intersected genes were then subjected to GO (Gene Ontology), and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and core genes were filtered using the PPI (Protein-Protein Interaction) network. Subsequently, relevant sepsis datasets (GSE65682, GSE28750, GSE54514, GSE67652, GSE69528, GSE95233) were downloaded from the GEO (Gene Expression Omnibus) database to perform bioinformatic validation of these core genes. Survival analysis was conducted to assess the prognostic value of the core genes, while ROC (Receiver Operating Characteristic) curves determined their diagnostic value, and a meta-analysis confirmed the accuracy of the RNA-seq data. Finally, we collected 5 blood samples (2 normal controls (NC); 2 sepsis; 1 SIRS (Systemic Inflammatory Response Syndrome), and used single-cell sequencing to assess the expression levels of the core genes in the different blood cell types. RESULTS: Integrating high-throughput sequencing with bioinformatics, this study identified two mitochondrial genes (COX7B, NDUFA4) closely linked with sepsis prognosis. Survival analysis demonstrated that patients with lower expression levels of COX7B and NDUFA4 exhibited a higher day survival rate over 28 days, inversely correlating with sepsis mortality. ROC curves highlighted the significant sensitivity and specificity of both genes, with AUC values of 0.985 for COX7B and 0.988 for NDUFA4, respectively. Meta-analysis indicated significant overexpression of COX7B and NDUFA4 in the sepsis group in contrast to the normal group (P < 0.01). Additionally, single-cell RNA sequencing revealed predominant expression of these core genes in monocytes-macrophages, T cells, and B cells. CONCLUSION: The mitochondrial-associated genes (MiAGs) COX7B and NDUFA4 are intimately linked with the prognosis of sepsis, offering potential guidance for research into the mechanisms underlying sepsis.

A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development.

The mitochondrial genome transcribes 13 mRNAs coding for well-known proteins essential for oxidative phosphorylation. We demonstrate here that cytochrome b (CYTB), the only mitochondrial-DNA-encoded transcript among complex III, also encodes an unrecognized 187-amino-acid-long protein, CYTB-187AA, using the standard genetic code of cytosolic ribosomes rather than the mitochondrial genetic code. After validating the existence of this mtDNA-encoded protein arising from cytosolic translation (mPACT) using mass spectrometry and antibodies, we show that CYTB-187AA is mainly localized in the mitochondrial matrix and promotes the pluripotent state in primed-to-naive transition by interacting with solute carrier family 25 member 3 (SLC25A3) to modulate ATP production. We further generated a transgenic knockin mouse model of CYTB-187AA silencing and found that reduction of CYTB-187AA impairs females' fertility by decreasing the number of ovarian follicles. For the first time, we uncovered the novel mPACT pattern of a mitochondrial mRNA and demonstrated the physiological function of this 14th protein encoded by mtDNA.

Distribution of mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes variants associated with hearing loss in Southwestern China.

BACKGROUND: Maternally inherited hearing loss has been associated with mitochondrial genes, including MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE. Among these genes, MT-RNR1 is known to be a hotspot for pathogenic variants related to aminoglycoside ototoxicity and nonsyndromic hearing loss. However, the frequency and spectrum of variants in these genes, particularly in multi-ethnic hearing loss patients from Southwestern China, are still not fully understood. METHODS: In this study, we enrolled 460 hearing loss patients from various ethnic backgrounds (Han, Yi, Dai, Hani, etc.) in Southwestern China. Next-generation sequencing was used to analyze the mitochondrial MT-RNR1, MT-TL1, MT-TS1, MT-TK and MT-TE genes. Subsequently, bioinformatical methods were employed to evaluate the identified variants. RESULTS: Among the patients with hearing loss, we identified 70 variants in MT-RNR1 (78.6 %, 55/70), MT-TL1 (4.3 %, 3/70), MT-TS1 (4.3 %, 3/70), MT-TK (7.1 %, 5/70) and MT-TE (5.7 %, 4/70) genes. We found that 15 variants were associated with hearing loss, including m.1555 A > G and m.1095 T > C. Additionally, we discovered three reported mitochondrial variants (m.676 G > A, m.7465 insC, and m.7474 A > G) newly correlated with hearing loss. Notably, certain pathogenic variants, such as m.1555 A > G, displayed non-consistent distributions among the multi-ethnic patients with hearing loss. Furthermore, the number of variants associated with hearing loss was higher in the Sinitic group (n = 181) and Tibeto-Burman group (n = 215) compared to the Kra-Dai group (n = 38) and Hmong-Mien group (n = 26). CONCLUSIONS: This present study revealed the distribution of mitochondrial variants linked to hearing loss across various ethnic groups in Southwestern China. These data suggest a potential correlation between the distribution of mitochondrial variants associated with hearing loss and ethnic genetic backgrounds.

Unveiling mitochondrial and ribosomal gene deregulation and tumor microenvironment dynamics in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant clonal hematopoietic disease with a poor prognosis. Understanding the interaction between leukemic cells and the tumor microenvironment (TME) can help predict the prognosis of leukemia and guide its treatment. Re-analyzing the scRNA-seq data from the CSC and G20 cohorts, using a Python-based pipeline including machine-learning-based scVI-tools, recapitulated the distinct hierarchical structure within the samples of AML patients. Weighted correlation network analysis (WGCNA) was conducted to construct a weighted gene co-expression network and to identify gene modules primarily focusing on hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), and natural killer (NK) cells. The analysis revealed significant deregulation in gene modules associated with aerobic respiration and ribosomal/cytoplasmic translation. Cell-cell communications were elucidated by the CellChat package, revealing an imbalance of activating and inhibitory immune signaling pathways. Interception of genes upregulated in leukemic HSCs & MPPs as well as in NKG2A-high NK cells was used to construct prognostic models. Normal Cox and artificial neural network models based on 10 genes were developed. The study reveals the deregulation of mitochondrial and ribosomal genes in AML patients and suggests the co-occurrence of stimulatory and inhibitory factors in the AML TME.

Identification of four mitochondria-related genes in sepsis based on RNA sequencing technology.

OBJECTIVES: The purpose of this study was to identify and analyze the mitochondrial genes associated with sepsis patients in order to elucidate the underlying mechanism of sepsis immunity and provide new ideas for the clinical treatment of sepsis. METHODS: The hospitalized cases of sepsis (n = 20) and systemic inflammatory response syndrome (SIRS) (n = 12) admitted to the Emergency Intensive Care Unit (EICU) of the Affiliated Hospital of Southwest Medical University from January 2019 to December 2019 were collected consecutively. RNA-seq was used to sequence the RNA (mRNA) of peripheral blood cells. Bioinformatics techniques were used to screen and identify differentially expressed RNAs, with an absolute value of fold change (FC) greater than or equal to 1.2 and a false discovery rate (FDR) less than 0.05. At the same time, mitochondrial genes were obtained from the MitoCarta 3.0 database. Differential genes were then intersected with mitochondrial genes. The resulting crossover genes were subjected to GO, KEGG, and PPI analysis. Subsequently, the GSE65682 dataset was downloaded from the GEO database for survival analysis to assess the prognostic value of core genes, and GSE67652 was downloaded for ROC curve analysis to validate the diagnostic value of core genes. Finally, the localization of core genes was clarified through 10X single-cell sequencing. RESULTS: The crossing of 314 sepsis differential genes and 1136 mitochondrial genes yielded 28 genes. GO and KEGG analysis showed that the crossover genes were mainly involved in the mitochondrion, mitochondrial matrix, and mitochondrial inner membrane. Survival analysis screened four genes that were significantly negatively associated with the prognosis of sepsis, namely FIS1, FKBP8, GLRX5, and GUK1. A comparison of peripheral blood RNA-seq results between the sepsis group and the SIRS group showed that the expression levels of these four genes were significantly decreased in the sepsis group compared to the SIRS group. ROC curve analysis based on GSE67652 indicates these four genes' high sensitivity and specificity for sepsis detection. Additionally, single-cell RNA sequencing found that the core genes were mainly expressed in macrophages, T cells, and B cells. CONCLUSIONS: Mitochondria-related genes (FIS1, FKBP8, GLRX5, GUK1) were underexpressed in the sepsis group, negatively correlated with survival, and mainly distributed in immune cells. This finding may guide studying the immune-related mechanisms of sepsis. This study protocol was reviewed by the Ethics Committee of the Affiliated Hospital of Southwest Medical University (ethics number: KY2018029), the clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019.

The mitochondria-related gene risk mode revealed p66Shc as a prognostic mitochondria-related gene of glioblastoma.

Numerous studies have highlighted the pivotal role of mitochondria-related genes (MRGs) in the initiation and progression of glioblastoma (GBM). However, the specific contributions of MRGs coding proteins to GBM pathology remain incompletely elucidated. The identification of prognostic MRGs in GBM holds promise for the development of personalized targeted therapies and the enhancement of patient prognosis. We combined differential expression with univariate Cox regression analysis to screen prognosis-associated MRGs in GBM. Based on the nine MRGs, the hazard ratio model was conducted using a multivariate Cox regression algorithm. SHC-related survival, pathway, and immune analyses in GBM cohorts were obtained from the Biomarker Exploration of the Solid Tumor database. The proliferation and migration of U87 cells were measured by CCK-8 and transwell assay. Apoptosis in U87 cells was evaluated using flow cytometry. Confocal microscopy was employed to measure mitochondrial reactive oxygen species (ROS) levels and morphology. The expression levels of SHC1 and other relevant proteins were examined via western blotting. We screened 15 prognosis-associated MRGs and constructed a 9 MRGs-based model. Validation of the model's risk score confirmed its efficacy in predicting the prognosis of patients with GBM. Furthermore, analysis revealed that SHC1, a constituent MRG of the prognostic model, was upregulated and implicated in the progression, migration, and immune infiltration of GBM. In vitro experiments elucidated that p66Shc, the longest isoform of SHC1, modulates mitochondrial ROS production and morphology, consequently promoting the proliferation and migration of U87 cells. The 9 MRGs-based prognostic model could predict the prognosis of GBM. SHC1 was upregulated and correlated with the prognosis of patients by involvement in immune infiltration. Furthermore, in vitro experiments demonstrated that p66Shc promotes U87 cell proliferation and migration by mediating mitochondrial ROS production. Thus, p66Shc may serve as a promising biomarker and therapeutic target for GBM.

The mechanism of mitochondrial metabolic gene PMAIP1 involved in Alzheimer's disease process based on bioinformatics analysis and experimental validation.

OBJECTIVES: This study explored novel biomarkers that can affect the diagnosis and treatment in Alzheimer's Disease (AD) related to mitochondrial metabolism. METHODS: The authors obtained the brain tissue datasets for AD from the Gene Expression Omnibus (GEO) and downloaded the mitochondrial metabolism-related genes set from MitoCarta 3.0 for analysis. Differentially Expressed Genes (DEGs) were screened using the "limma" R package, and the biological functions and pathways were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The LASSO algorithm was used to identify the candidate center genes and validated in the GSE97760 dataset. PMAIP1 with the highest diagnostic value was selected and its effect on the occurrence of AD by biological experiments. RESULTS: A sum of 364 DEGs and 50 hub genes were ascertained. GO and KEGG enrichment analysis demonstrated that DEGs were preponderantly associated with cell metabolism and apoptosis. Five genes most associated with AD as candidate central genes by LASSO algorithm analysis. Then, the expression level and specificity of candidate central genes were verified by GSE97760 dataset, which confirmed that PMAIP1 had a high diagnostic value. Finally, the regulatory effects of PMAIP1 on apoptosis and mitochondrial function were detected by siRNA, flow cytometry and Western blot. siRNA-PMAIP1 can alleviate mitochondrial dysfunction and inhibit cell apoptosis. CONCLUSION: This study identified biomarkers related to mitochondrial metabolism in AD and provided a theoretical basis for the diagnosis of AD. PMAIP1 was a potential candidate gene that may affect mitochondrial function in Hippocampal neuronal cells, and its mechanism deserves further study.

The efficacy of single mitochondrial genes at reconciling the complete mitogenome phylogeny-a case study on dwarf chameleons.

Although genome-scale data generation is becoming more tractable for phylogenetics, there are large quantities of single gene fragment data in public repositories and such data are still being generated. We therefore investigated whether single mitochondrial genes are suitable proxies for phylogenetic reconstruction as compared to the application of full mitogenomes. With near complete taxon sampling for the southern African dwarf chameleons (Bradypodion), we estimated and compared phylogenies for the complete mitogenome with topologies generated from individual mitochondrial genes and various combinations of these genes. Our results show that the topologies produced by single genes (ND2, ND4, ND5, COI, and COIII) were analogous to the complete mitogenome, suggesting that these genes may be reliable markers for generating mitochondrial phylogenies in lieu of generating entire mitogenomes. In contrast, the short fragment of 16S commonly used in herpetological systematics, produced a topology quite dissimilar to the complete mitogenome and its concatenation with ND2 weakened the resolution of ND2. We therefore recommend the avoidance of this 16S fragment in future phylogenetic work.

Identification of key mitochondria-related genes and their relevance to the immune system linking Parkinson's disease and primary Sjögren's syndrome through integrated bioinformatics analyses.

BACKGROUND: Mitochondria are the metabolic hubs of cells, regulating energy production and antigen presentation, which are essential for activation, proliferation, and function of immune cells. Recent evidence indicates that mitochondrial antigen presentation may have an impact on diseases such as Parkinson's disease (PD) and autoimmune diseases. However, there is limited knowledge about the mechanisms that regulate the presentation of mitochondrial antigens in these diseases. METHODS: In the current study, RNA sequencing was performed on labial minor salivary gland (LSG) from 25 patients with primary Sjögren's syndrome (pSS) and 14 non-pSS aged controls. Additionally, we obtained gene expression omnibus datasets associated with PD patients from NCBI Gene Expression Omnibus (GEO) databases. Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE and Spearman correlations were conducted to explore the association between mitochondrial related genes and the immune system. Furthermore, we applied weighted Gene Co-expression Network Analysis (WGCNA) to identify hub mitochondria-related genes and investigate the correlated networks in both diseases. Single cell transcriptome analysis, immunohistochemical (IHC) staining and quantitative real-time PCR (qRT-PCR) were used to verify the activation of the hub mitochondria-related pathway. Pearson correlations and the CIBERSORT algorithms were employed to further reveal the correlation between hub mitochondria-related pathways and immune infiltration. RESULTS: The transcriptome analysis revealed the presence of overlapping mitochondria-related genes and mitochondrial DNA damage in patients with pSS and PD. Reactive oxygen species (ROS), the senescence marker p53, and the inflammatory markers CD45 and Bcl-2 were found to be regionally distributed in LSGs of pSS patients. WGCNA analysis identified the STING pathway as the central mitochondria-related pathway closely associated with the immune system. Single cell analysis, IHC staining, and qRT-PCR confirmed the activation of the STING pathway. Subsequent, bioinformatic analysis revealed the proportion of infiltrating immune cells in the STING-high and STING-low groups of pSS and PD. Furthermore, the study demonstrated the association of the STING pathway with innate and adaptive immune cells, as well as functional cells, in the immune microenvironment of PD and pSS. CONCLUSION: Our study uncovered a central pathway that connects mitochondrial dysfunction and the immune microenvironment in PD and pSS, potentially offering valuable insights into therapeutic targets for these conditions.

SynGenes: a Python class for standardizing nomenclatures of mitochondrial and chloroplast genes and a web form for enhancing searches for evolutionary analyses.

BACKGROUND: The reconstruction of the evolutionary history of organisms has been greatly influenced by the advent of molecular techniques, leading to a significant increase in studies utilizing genomic data from different species. However, the lack of standardization in gene nomenclature poses a challenge in database searches and evolutionary analyses, impacting the accuracy of results obtained. RESULTS: To address this issue, a Python class for standardizing gene nomenclatures, SynGenes, has been developed. It automatically recognizes and converts different nomenclature variations into a standardized form, facilitating comprehensive and accurate searches. Additionally, SynGenes offers a web form for individual searches using different names associated with the same gene. The SynGenes database contains a total of 545 gene name variations for mitochondrial and 2485 for chloroplasts genes, providing a valuable resource for researchers. CONCLUSIONS: The SynGenes platform offers a solution for standardizing gene nomenclatures of mitochondrial and chloroplast genes and providing a standardized search solution for specific markers in GenBank. Evaluation of SynGenes effectiveness through research conducted on GenBank and PubMedCentral demonstrated its ability to yield a greater number of outcomes compared to conventional searches, ensuring more comprehensive and accurate results. This tool is crucial for accurate database searches, and consequently, evolutionary analyses, addressing the challenges posed by non-standardized gene nomenclature.