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• Although horizontal gene transfer (HGT) is common in angiosperm mitochondrial DNAs (mtDNAs), few cases of functional foreign genes have been identified. The one outstanding candidate for large-scale functional HGT is the holoparasite Lophophytum mirabile, whose mtDNA has lost most native genes but contains intact foreign homologs acquired from legume host plants. • To investigate the extent to which this situation results from functional replacement of native by foreign genes, functional mitochondrial gene transfer to the nucleus, and/or loss of mitochondrial biochemical function in the context of extreme parasitism, we examined the Lophophytum mitochondrial and nuclear transcriptomes by deep paired-end RNA sequencing. • Most foreign mitochondrial genes in Lophophytum are highly transcribed, accurately spliced, and efficiently RNA edited. By contrast, we found no evidence for functional gene transfer to the nucleus or loss of mitochondrial functions in Lophophytum. Many functional replacements occurred via the physical replacement of native genes by foreign genes. Some of these events probably occurred as the final act of HGT itself. • Lophophytum mtDNA has experienced an unprecedented level of functional replacement of native genes by foreign copies. This raises important questions concerning population-genetic and molecular regimes that underlie such a high level of foreign gene takeover.

Succinate is identified as a metabolite in innate immune signalling, which leads to enhanced interleukin-1β production during inflammation. Succinate is an innate immunity signal The bacterial endotoxin lipopolysaccharide activates macrophages, as part of the innate immunity response, by inducing a shift from oxidative to glycolytic metabolism. Gillian Tannahill et al . show here that lipopolysaccharide increases levels of the tricarboxylic acid cycle intermediate succinate in macrophages through a metabolic process not previously reported in macrophages, the 'GABA shunt'. Succinate in turn drives the key pro-inflammatory cytokine interleukin-1β. Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis 1 . Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the ‘GABA (γ-aminobutyric acid) shunt’ pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.

Mitochondria play a pivotal role in energy production, metabolism, and cellular signaling, serving as key regulators of cellular functions, including differentiation and tissue-specific adaptation. The interplay between mitochondria and the nucleus is crucial for coordinating these processes, particularly through the supply of metabolites for epigenetic modifications that facilitate nuclear-mitochondrial interactions. To investigate tissue-specific mitochondrial adaptations at the molecular level, we conducted RNA sequencing data analyses of kidney, heart, brain, and ovary tissues of female buffaloes, focusing on variations in mitochondrial gene expression related to amino acid metabolism. Our analysis identified 82 nuclear-encoded mitochondrial transcripts involved in amino acid metabolism, with significant differential expression patterns across all tissues. Notably, the heart, brain, and kidney-tissues with higher energy demands-exhibited elevated expression levels compared to the ovary. The kidney displayed unique gene expression patterns, characterized by up-regulation of genes involved in glyoxylate metabolism and amino acid catabolism. In contrast, comparative analysis of the heart and kidney versus the brain revealed shared up-regulation of genes associated with fatty acid oxidation. Gene ontology and KEGG pathway analyses confirmed the enrichment of genes in pathways related to amino acid degradation and metabolism. These findings highlight the tissue-specific regulation of mitochondrial gene expression linked to amino acid metabolism, reflecting mitochondrial adaptations to the distinct metabolic and energy requirements of different tissues in buffalo. Importantly, our results underscore the relevance of mitochondrial adaptations not only for livestock health but also for understanding metabolic disorders in humans. By elucidating the molecular mechanisms of mitochondrial function and their tissue-specific variations, this study provides insights that could inform breeding strategies for enhanced livestock productivity and contribute to therapeutic approaches for human metabolic diseases. Thus, our findings illustrate how mitochondria are specialized in a tissue-specific manner to optimize amino acid utilization and maintain cellular homeostasis, with implications for both animal welfare and human health.

Purpose This study aims to reveal the mechanism of fibroblast‐related mitochondrial genes on keloid formation and explore promising signature genes for keloid diagnosis. Method The distribution of fibroblasts between the keloid sample and control sample based on three keloid datasets, followed by the differentially expressed genes (DEGs) investigation and associated enrichment analysis. Then, hub genes were explored based on DEGs, mitochondrial genes from an online database, as well as fibroblast‐related genes that were revealed by WCGNA. Subsequently, signature genes were screened through machine learning, and their diagnostic value was validated by nomogram. Moreover, the targeted drugs and related transcriptional regulation of these genes were analyzed. Finally, the verification analysis was performed on signature genes using qPCR analysis. Result A total of totally 329 DEGs were revealed based on three datasets, followed by enrichment analysis. WGCNA revealed a total of 258 fibroblast‐related genes, which were primarily assembled in functions like muscle tissue development. By using machine learning, we screened four signature genes (ACSF2, ALDH1B1, OCIAD2, and SIRT4) based on eight hub genes (fibroblast‐related mitochondrial genes). Nomogram and validation analyses confirmed the well‐diagnostic performance of these four genes in keloid. Immune infiltration and drug correlation analyses showed that SIRT4 was significantly associated with immune cell type 2 T helper cells and molecular drug cyclosporin. All these findings provided new perspectives for the clinical diagnosis and therapy of keloid. Conclusion The fibroblast‐related mitochondrial genes including SIRT4, OCIAD2, ALDH1B1, and ACSF2 were novel signature genes for keloid diagnosis, offering novel targets and strategies for diagnosis and therapy of keloid.

Mitochondrial dysfunction has been implicated in the pathogenesis of major depressive disorder (MDD); however, the causal contributions of specific mitochondrial genes across regulatory layers remain unclear. We integrated genome-wide association study summary statistics from the Psychiatric Genomics Consortium and FinnGen with quantitative-trait-locus (QTL) datasets for DNA methylation, gene expression (eQTL), and protein abundance. Mitochondrial genes were annotated using the MitoCarta3.0 database. Summary-based Mendelian randomization and Bayesian colocalization were applied to assess causal relationships, with colocalization determined by the posterior probability of a shared causal variant (PPH4), and the false discovery rate used for multiple-testing correction. Brain-specific effects were evaluated using Genotype-Tissue Expression eQTL data. Prioritized genes were ranked based on cross-omics consistency and replication evidence. Five mitochondrial genes were prioritized. showed consistent associations across methylation, transcription, and protein levels, with hypermethylation at cg24503712 linked to reduced expression and a lower risk of MDD (Tier 1). (Tier 2) demonstrated protective effects at both the transcript and protein levels. , , and (Tier 3) exhibited consistent but complex regulatory patterns. Several signals were replicated in brain tissues, including in the caudate and in the cortex. This study provides multi-omics evidence for the causal involvement of mitochondrial genes in MDD. and emerged as key candidates, offering promising targets for future mechanistic research and therapeutic development.

Background Angiosperms are the largest plant group and play an essential role in the biosphere. Phylogenetic relationships of many families and orders remain contentious, and, in an attempt to address these, we performed the most extensive sampling of mitochondrial genes to date. Results We reconstructed a seed plant phylogenetic framework based on 41 mitochondrial protein-coding sequences (mtCDSs), representing 335 families and 63 orders with 481 angiosperm species. The results for major clades of angiosperms produced moderate to strong support (> 70% bootstrap) for more than 80% of nodes and strong support for most orders. Eight major nodes were supported, including the three paraphyletic ANA orders (Amborellales, Nymphaeales, and Austrobaileyales) and five major core-angiosperm clades. Chloranthales and Ceratophyllales are sister to the eudicots, whereas the monocots are sister to the magnoliids. Although well-supported, relationships within the asterids and rosids were in some cases unresolved or weakly supported, due to the low levels of variability detected in these genes. Conclusions Our results indicated that mitochondrial genomic data were effective at resolving deep node relationships of angiosperm phylogeny and thus represent an important resource for phylogenetics and evolutionary studies of angiosperm.

Entomophthoroid fungi represent an ecologically important group of fungal pathogens on insects. Here, the whole mitogenome of Conidiobolus heterosporus , one of the entomophthoroid fungi, was described and compared to those early branching fungi with available mitogenomes. The 53,364-bp circular mitogenome of C. heterosporus contained two rRNA genes, 14 standard protein-coding genes, 26 tRNA genes, and three free-standing ORFs. Thirty introns interrupted nine mitochondrial genes. Phylogenetic analysis based on mitochondrion-encoded proteins revealed that C. heterosporus was most close to Zancudomyces culisetae in the Zoopagomycota of basal fungi. Comparison on mitogenomes of 23 basal fungi revealed great variabilities in terms of mitogenome conformation (circular or linear), genetic code (codes 1, 4, or 16), AT contents (53.3 – 85.5%), etc. These mitogenomes varied from 12.0 to 97.3 kb in sizes, mainly due to different numbers of genes and introns. They showed frequent DNA rearrangement events and a high variability of gene order, although high synteny and conserved gene order were also present between closely related species. By reporting the first mitogenome in Entomophthoromycotina and the second in Zoopagomycota , this study greatly enhanced our understanding on evolution of basal fungi.

The physiological well-being of buffaloes, encompassing phenotypic traits, reproductive health, and productivity, depends on their energy status. Mitochondria, the architects of energy production, orchestrate a nuanced interplay between nuclear and mitochondrial domains. Oxidative phosphorylation complexes and associated proteins wield significant influence over metabolic functions, energy synthesis, and organelle dynamics, often linked to tissue-specific pathologies. The unexplored role of ATP synthase in buffalo tissues prompted a hypothesis: in-depth exploration of nuclear-derived mitochondrial genes, notably ATP synthase, reveals distinctive tissue-specific diversity. RNA extraction and sequencing of buffalo tissues (kidney, heart, brain, and ovary) enabled precise quantification of nuclear-derived mitochondrial protein gene expression. The analysis unveiled 24 ATP synthase transcript variants, each with unique tissue-specific patterns. Kidney, brain, and heart exhibited elevated gene expression compared to ovaries, with 10, 8, and 19 up-regulated genes, respectively. The kidney showed 3 and 12 down-regulated genes compared to the brain and heart. The heart–brain comparison highlighted ten highly expressed genes in ATP synthase functions. Gene ontology and pathway analyses revealed enriched functions linked to ATP synthesis and oxidative phosphorylation, offering a comprehensive understanding of energy production in buffalo tissues. This analysis enhances understanding of tissue-specific gene expression, emphasizing the influence of energy demands. Revealing intricate links between mitochondrial gene expression and tissue specialization in buffaloes, it provides nuanced insights into tissue-specific expression of nuclear-encoded mitochondrial protein genes, notably ATP synthase, advancing the comprehension of buffalo tissue biology.

Invertebrate mitogenomes are generally fixed with formal 37 genes: 13 PCGs encoded subunits of OXPHOS, 2 ribosomal RNA (rRNA) functional in the translation of these PCGs and 22 transfer RNA (tRNA) genes. The order of these genes varies greatly among organisms and named rearrangement. Rearrangement patterns of mitochondrial genomes may shed light on mutation processes and evolutionary relationships of organisms. Mitochondrial gene organization is highly variable among Acari, so rearrangement is a very common mitogenomic pattern in this group. In this study, 258 unique Acari (Acariformes + Parasitiformes) mitogenomes were downloaded from NCBI and studied about rearrangement patterns. Sixty-seven mitotypes were determined among Acari and the most rearranged genes were trnL1 and nad2. Following that, trnI, trnS1, trnN, trnE, trnT, and trnP genes are remarkably mobile (RF > 95%). Conversely, atp6 , cox3 , trnG, and cytb genes also appears to be quite stable (RF < 20%). Within Acari, mean distance calculations are varied from 1.210 in atp8 to 0.155 in rrnS. Contrary to expectations, among Acari mobile tRNA genes appear to be conserved in sequences, whereas PCGs have higher distance values and seem to be mutated. Consistently, tRNA genes seem saturated, but some PCGs ( atp6 , cox genes, cytb , nad1 , and nad6 ) are not saturated. These values do not correlate with each other ( p  > 0.005). This discrepancy may indicate that the genes were rearranged after mutation load; consistent with this, DAMBE saturation values are also not correlated with RF values. Parasitiformes mitogenomes are more mobile than Acariformes mitogenomes and may be under the effect of selective sweeping.

Gastric cancer (GC) is a common digestive system cancer, characterized by a significant mortality rate. Mitochondria is an indispensable organelle in eukaryotic cells. It was previously revealed that a series of nucleus-encoded mitochondrial genes (NMG) mutations and dysfunctions potentially contribute to the initiation and progression of GC. However, the correlation between NMG mutations and survival outcomes for GC patients is still unclear. In this study, NMG expression profile and clinical information in GC samples were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Through consistent clustering and functional enrichment analysis, we have identified three NMG clusters and three gene clusters that are associated with patterns of immune cell infiltration. Prognostic genes were identified through Univariate Cox regression analysis. The principal component analysis was conducted to set up a scoring system. Subsequently, the Single‑cell RNA sequencing (scRNA-seq) data of GC patients and cancer cell drug sensitivity data were retrieved from the GEO database. Patients with high NMG scores exhibited increased microsatellite instability status and a heightened tumor mutation rate compared to those with low NMG scores. Survival analysis revealed that GC samples with high NMG scores could achieve a better prognosis. Additionally, These patients were observed to be more responsive to immunotherapy. Moreover, we delved into prognostic genes at the level of single cells, revealing that MRPL4 and MRPL37 exhibit high expression in epithelial cells, while TPM1 demonstrates high expression in tissue stem cells. Utilizing cancer cell drug sensitivity data from the Drug Sensitivity in Cancer (GDSC) database, we noted a heightened sensitivity to chemotherapy in the high NMG group. Furthermore, we discovered a significant enrichment of cuproptosis-related genes in clusters with high NMG scores. Consequently, employing the scoring system could facilitate the prediction of GC patients’ sensitivity to cuproptosis-induced therapy. Our study confirmed the potency of this scoring system as a therapeutic response biomarker for gastric cancer, potentially informing clinical treatment strategies.