Search Results (189)

Atherosclerotic cardiovascular disease (ASCVD) is increasingly recognized not merely as a lipid-storage disorder but as a chronic, lipid-driven inflammatory condition of the arterial wall. Despite the widespread use of statins and other lipid-lowering therapies, a substantial “residual inflammatory risk” persists, propelling the search for targeted immunopharmacological interventions. At the forefront of this inflammatory cascade is the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which serves as a central orchestrator of vascular inflammation by linking metabolic dysregulation to the innate immune response. Atherogenic danger signals—such as oxidized low-density lipoprotein (ox-LDL) and cholesterol crystals—trigger NLRP3 activation through reactive oxygen species (ROS) generation, lysosomal rupture, and potassium efflux. This, in turn, drives the maturation of pro-inflammatory cytokines (IL-1β and IL-18) and initiates macrophage pyroptosis. In this review, we systematically evaluate the immunomodulatory potential of natural products—both complex extracts and single bioactive compounds—in inhibiting the NLRP3 inflammasome axis. We detail the pharmacological mechanisms by which these natural agents intercept inflammatory signaling at multiple stages: suppressing TLR4/NF-κB-mediated priming, scavenging mitochondrial ROS, and restoring autophagic flux via AMPK/mTOR pathways to prevent inflammasome assembly. By critically analyzing these pathways, we highlight natural product-derived inhibitors as a promising class of immunomodulators capable of attenuating atherosclerotic progression and addressing the persistent challenge of residual inflammatory risk. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article

Corydalis impatiens (Papaveraceae) is a traditional Tibetan medicinal plant (“Pa Xia Ga”) whose mitochondrial genome evolution remains unexplored, particularly in the context of high-altitude adaptation. This study presents the first complete mitochondrial genome sequence of an alpine Corydalis species to establish a comparative framework with the lowland congener C. pauciovulata for investigating environment-associated mitochondrial evolution. Using Illumina sequencing and reference-guided assembly, we characterized a 688,959 bp circular genome containing 74 genes, with GC content variations reflecting functional compartmentalization—elevated in structural RNA genes (tRNAs: 51.24%; rRNAs: 52.79%) versus protein-coding genes (44.19%). We identified 719 RNA editing sites concentrated in NADH dehydrogenase genes, suggesting post-transcriptional optimization of respiratory complex I under hypoxic conditions. The genome harbors 50 dispersed repeats (7.50%) and 67 SSRs with A-rich predominance, providing species-specific markers for authenticating “Pa Xia Ga” in Tibetan medicine quality control. Phylogenomic analysis confirms close affinity with C. pauciovulata while resolving intrageneral relationships within Ranunculales. These findings establish a dual-reference system for distinguishing conserved genus-level features from altitude-associated adaptations, enabling future comparative mitogenomics across the 465-species genus and supporting DNA-based medicinal plant identification. Full article

Mitochondria are a key organelle in maintaining metabolic homeostasis. It not only generates most of the cell’s energy through oxidative phosphorylation but also acts as a complex sensor of the redox state and oxygen in the cell. This review thoroughly analyzes the interactions among mitochondrial iron metabolism, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation (LPO), the triggering factors of ferroptosis, an iron-dependent form of programmed cell death. We point out research showing that intrinsic mitochondrial machinery, such as iron–sulfur (Fe-S) cluster assembly and heme metabolism, is both an important cofactor and a master regulator. If these processes are disrupted, they can lead to ferroptosis. Unlike views that focus on the cytosol, we explain that the stability of Fe-S clusters in complexes such as aconitase and respiratory Complex I is crucial for preventing electron leakage and excessive mtROS formation. The Fenton reaction and its direct effect on cardiolipin (CL) oxidation in the inner membrane of mitochondria is a central event in cardiometabolic diseases. Its peroxidation and breakdown make the organelle very unstable and lead to cell death though Ca²⁺ overload and a significantly decreased reduced/oxidized glutathione ratio. Additionally, the functions of essential iron transporters and glutathione homeostasis are examined, and their dysregulation is correlated with ferroptosis-associated progression of cardiometabolic and neurodegenerative disorders, such as obesity and Alzheimer’s disease. This review focused on the need to revisit the classic bioenergetic core of the mitochondria as a key player in the pathophysiology of metabolic and neurodegenerative diseases. Full article

Background: Plant mitochondrial genomes exhibit extreme variation in size and structure while maintaining a conserved set of core protein-coding genes. This combination of structural diversity and functional conservation provides valuable insights into evolutionary processes such as genome expansion, rearrangement, and intracellular DNA transfer. Curcuma longa, an economically and medicinally important species in the genus Curcuma (Zingiberaceae), has not yet been studied in terms of the organization and evolution of its mitochondrial genome. Methods: In this study, we assembled and annotated the mitochondrial and plastid genomes of C. longa using third-generation HiFi sequencing data, systematically analyzing their genomic structure, repetitive sequence content, and features of sequence transfer between nuclear and organellar genomes. Results: The mitochondrial genome of C. longa was assembled as a complex, network-like structure consisting of 12 contigs with a total length of approximately 7.7 Mb, making it one of the largest mitochondrial genomes reported in monocots to date. Comparative analysis revealed significant differences in repeat types, abundance, and length distribution between the two organellar genomes. Additionally, extensive intracellular DNA transfer events were identified among the nuclear, mitochondrial, and plastid genomes. Conclusions: Overall, this study provides the first comprehensive report on the giant mitochondrial genome of C. longa, detailing its structural organization, repeat content, and intergenomic transfers. These findings lay a foundation for understanding mitochondrial genome evolution in Curcuma and offer broader insights into the mechanisms driving extreme mitochondrial genome expansion in angiosperms and monocots specifically. Full article

Recent evolutionary genetics and molecular characterisation of Cryptolestes (Ganglbauer) stored grain pest beetle species revealed gaps in public DNA databases that resulted in molecular diagnostic inconsistencies in publicly available sequence databases. We report the characterisation of mitochondrial DNA cytochrome oxidase I (mtCOI) genes from specimens intercepted during Australia’s border biosecurity inspections, and surveys of public mtCOI gene sequences, for Cryptolestes species status re-assessment. We identified and characterised a new putative Cryptolestes species (C. sp. ‘WTT-2016’) and demonstrated the close evolutionary relationships between C. ferrugineus (Stephens)/C. pusilloides (Steel and Howe) and between C. pusillus (Schonherr) and the previously identified C. sp. ‘WTT-2013’ cryptic species. Confusion between C. ferrugineus, C. pusiolloides, C. pusillus, C. sp. ‘WTT-2013’, and C. sp. ‘WTT-2016’ highlighted a substantial and persistent taxonomic challenge within Cryptolestes, while low C. spartii (Curtis)/C. corticinus (Reitter) inter-specific genetic distances suggested they were the same species. Assembled and annotated mitochondrial DNA genomes (mitogenomes) of six Cryptolestes species identified assembly errors in published mitogenomes of C. ferrugineus and C. turcicus (Grouvelle) and misidentification of C. pusillus. Based on re-evaluation of genetic distances and phylogeny congruence, we proposed a Cryptolestes ‘operational species-level genetic gap’ at approximately 5% to help define Cryptolestes species boundaries, thereby contributing to improving agricultural biosecurity preparedness associated with this important stored grain beetle species. Our work also provides an evolutionary framework that will contribute to future understanding of ecological and environmental impact posed by this highly invasive cryptic beetle species complex. Full article

Background/Objectives: The retromer protein complex is involved in various physiological processes, especially endosomal trafficking, and its dysregulation has been linked to Alzheimer’s disease and Parkinson’s disease, as well as VPS35 knockout (KO), causing early embryonic lethality. We aimed to investigate the cellular consequences of VPS35 deficiency. Methods: To investigate the effects of VPS35 loss, we used CRISPR/Cas9 to generate VPS35 KO human embryonic kidney 293 (HEK293) cells. We analyzed changes in retromer component expression, cell proliferation, apoptosis, and mitochondrial dynamics using Western blotting, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and confocal microscopy. Results: VPS35 KO led to a significant reduction in cell proliferation and decreased expression of VPS29 and VPS26, both essential for retromer complex assembly. Consequently, retromer formation was impaired. Compared to control cells, KO cells exhibited elevated levels of cleaved caspase-3, poly(ADP-ribose) polymerase, cytochrome C, and p21, while the expression of Ki-67, CDK4, and cyclin D was reduced. Additionally, VPS35 deletion also promoted mitochondrial fragmentation, associated with increased expression of mitochondrial fission-related proteins. Finally, the rescue experiment using the human VPS35 gene confirmed that the recovery of VPS35 not only led to the recovery of the essential elements constituting the retromer but also the recovery of molecules related to the cell cycle, restoring cell death to a normal level. Conclusions: These findings suggest that VPS35 plays a critical role in cell growth and survival by modulating apoptosis, mitochondrial dynamics, and cell cycle progression. Full article

Background: Hemiboea yongfuensis is a recently discovered critically endangered species. It is exclusive to the limestone regions of Yongfu County, Guilin, Guangxi. Currently, there is a lack of mitogenome data for Hemiboea species, hindering the potential of disclosing the evolutionary processes of the mitochondrial genome, which has been far less assembled and shown to be complex in the plant kingdom. Moreover, it prevents potential applications of mitochondrial genome data in phylogenetics and plant adaption, breeding, and conservation. Results: In order to reveal the mitochondrial features and variations and explore the usefulness of mitochondrial genes in phylogenetics, in this study, we assembled the complete mitogenome of H. yongfuensis using PacBio HiFi long reads, and analyzed its codon usage bias, RNA editing sites, repetitive sequences, sequence lateral transfer, phylogenetic relationships, and synteny. The linear mitochondrial genome assembly we obtained has a length of 619,997 bp and a GC content of 43.63%. The assembly encompasses 61 genes, which include 37 protein-coding genes (PCGs), 21 transfer RNA (tRNA) genes, and 3 ribosomal RNA (rRNA) genes. Importantly, our analysis uncovered a significant presence of repetitive sequences with a high proportion of forward repeats in the mitogenome and significant transposition of sequences from the chloroplast to mitochondrion. Additionally, we revealed the codon usage characteristics of protein-coding genes and identified numerous RNA editing events. Furthermore, we assessed the collinearity of the species in the Gesneriaceae family and found rampant reorganizations. The phylogenetic analyses based on the mitochondrial PCGs for the entire Lamiales order show the monophyly of Gesneriaceae as well as other families and a general high phylogenetic resolution. Conclusions: Our study provides the first mitogenome data for H. yongfuensis and the genus Hemiboea, expanding the rapidly increasing but yet limited plant mitogenome resources. It enhances our understanding of the mitogenome and Lamiales evolution, whereas more potentials of the mitogenome data, such as its possible functions in adaptation to limestone habitats, conservation, and germplasm breeding, remain under-exploited. This first reported Hemiboea mitogenome in addition to more mitogenomes from the same and related species would shed further light on these unresolved issues in future studies. Full article

Mitochondrial respiratory supercomplexes are emerging as key regulators of bioenergetics, redox homeostasis, and metabolic plasticity in cancer. Their assembly enhances electron transport efficiency, limits reactive oxygen species production, and supports the high oxidative and biosynthetic demands of tumor growth. Cancer cells remodel supercomplex organization in response to hypoxia, nutrient limitation, and therapeutic stress, enabling rapid metabolic adaptation. Multiple assembly factors—including COX subunits, HIGD1A/2A, COX7A2L (SCAF1), cardiolipin remodeling enzymes, and Complex I assembly factors such as NDUFAF1 and NDUFAF2—contribute to supercomplex stabilization and can be dysregulated in malignancy. Alterations in these factors enhance respiratory flexibility and therapy resistance, particularly in aggressive tumors such as glioblastoma. However, critical gaps remain, including incomplete understanding of the molecular mechanisms controlling supercomplex assembly and remodeling, limited validation of functional findings in primary patient-derived cells or clinical samples, and uncertainty regarding the contribution of supercomplex to therapy resistance and metabolic adaptation across tumor types. Advances in structural biology and functional imaging have uncovered tumor-specific vulnerabilities within supercomplex architecture that may be exploited therapeutically. Targeting supercomplex assembly, cardiolipin–protein interactions, or electron flux through individual supercomplex modules represents a promising approach to disrupt cancer metabolism and sensitize tumors to treatment. This review synthesizes current knowledge on supercomplex regulation, function, and therapeutic potential in cancer, and outlines key unanswered questions that remain to be addressed. Full article

Background/Objectives: We have previously demonstrated that fatty acid oxidation (FAO) enzymes physically and functionally interact with electron transfer chain supercomplexes (ETC-SC) at two contact points. The FAO trifunctional protein (TFP) and electron transfer flavoprotein dehydrogenase (ETFDH) interact with the NADH⁺-binding domain of ETC complex I (com I) and the core 2 subunit of complex III (com III), respectively. In addition, the FAO enzyme very-long-chain acyl-CoA dehydrogenase (VLCAD) interacts with TFP. These interactions define a functional FAO-ETC macromolecular complex (FAO-ETC MEC) in which FAO-generated NADH⁺ and FADH₂ can safely transfer electron equivalents to ETC in order to generate ATP. Methods: In this study, we use multiple mitochondrial functional studies to demonstrate the effect of added VLCAD protein on mutant mitochondria. Results: We demonstrate that heart mitochondria from a VLCAD knockout (KO) mouse exhibit disrupted supercomplexes, with significantly reduced levels of TFPα and TFPβ subunits, electron transfer flavoprotein a-subunit (ETFα), and NDUFV2 subunit of com I in the FAO-ETC MEC. In addition, the activities of individual oxidative phosphorylation (OXPHOS) enzymes are decreased, as is the transfer of reducing equivalents from palmitoyl-CoA to ETC (FAO-ETC flux). However, the total amount of these proteins did not decrease in VLCAD KO animals. These results suggest that loss of VLCAD affects the interactions of FAO and ETC proteins in the FAO-ETC MEC. Reconstitution of VLCAD-deficient heart mitochondria with recombinant VLCAD improved the levels of FAO-ETC MEC proteins and enzyme activities, as well as restoring FAO-ETC flux. It also reduced mitochondrial ROS levels, previously demonstrated to be elevated in VLCAD-deficient mitochondria. In contrast, incubation of VLCAD KO mitochondria with two VLCADs with mutations in the C-terminal domain of the enzyme (A450P and L462P) did not restore FAO-ETC MECs. Conclusions: These results suggest that VLCAD is a necessary component of the FAO-ETC MEC and plays a major role in assembly of the macro-supercomplex. These studies provide evidence that both the level of enzyme and its structural confirmation are necessary to stabilize the FAO-ETC MEC. Full article

The assembly of telomere-to-telomere (T2T) genomes is essential for understanding genomic architecture, especially in fungal pathogens with complex karyotypes, such as Colletotrichum lini, causing flax anthracnose disease. This study provides optimized guidelines for the T2T genome assembly using Oxford Nanopore Technologies (ONT) R9.4.1 and R10.4.1 sequencing data processed with the Hifiasm 0.25.0 assembler (with --ont module). We analyzed ONT sequencing data for four C. lini strains and compared basecalling tools (Guppy and Dorado), read filtration strategies (quality thresholds Q10/Q15 and length cut-offs 5 kb/10 kb), and genome coverage levels from 5× to 160×. Our results demonstrated that Dorado-basecalled reads consistently had higher average quality, especially the R10.4.1 data, leading to improved telomere resolution and complete mitochondrial genome assembly. Moderate genome coverage (40–65×) combined with Q15 quality and 5 kb length filtration for R10.4.1 data, or Q10 and 5 kb for R9.4.1 data, produced the most contiguous and complete assemblies. Overfiltration of reads by length and quality or conversely excessive coverage (>90×) reduced assembly quality, causing fragmentation or erroneous chromosome merging. With optimized parameters of ONT R9.4.1 and R10.4.1 sequencing data preprocessing, Hifiasm efficiently generated T2T and near-T2T assemblies of C. lini genomes: 53.7–56.1 Mb length, 13–30 contigs, 12–13 chromosomes (including 3–12 T2T chromosomes), complete mitochondrial genome, and >98.5% BUSCO completeness. These findings provide a solid framework for ONT-based fungal genome assembly, facilitating future research on genomic variation and pathogenicity in Colletotrichum and related genera. Full article

Mitochondrial oxidative phosphorylation serves as a critical driving force in the progression of ovarian cancer. Recent studies have demonstrated that copper induces mitochondrial-dependent programmed cell death by directly binding to the thioacylated components of the tricarboxylic acid (TCA) cycle. The involvement of copper in OXPHOS complex IV, a rate-limiting step in the mitochondrial respiratory chain, suggests that the role of mitochondria in mediating copper-induced cell death can be further elucidated through the study of OXPHOS complex IV. The findings of this study indicate that the cuproptosis process in ovarian cancer, induced by Elesclomol, is associated with mitochondrial complex IV, with LRPPRC identified as a crucial factor. Following Elesclomol treatment of ovarian cancer cells, there was a notable increase in mitochondrial reactive oxygen species (ROS), a significant accumulation of the copper death marker protein DLAT, and a marked decrease in the lipoic acid synthesis-related protein FDX1. Furthermore, the expression levels of copper ion transporters ATP7B and CTR1, which are involved in the assembly and translation of complex IV, as well as the core subunit MTCO1 of complex IV, the copper chaperone protein SCO1, and the interacting protein LRPPRC, were significantly diminished. Inhibition of the IV-stabilizing protein LRPPRC in the ovarian cancer cell lines A2780 and SKOV3 through RNA interference resulted in increased sensitivity to Elesclomol. Concurrently, the expression levels of FDX1, LIAS, LIPT1, SCO1, and MTCO1 decreased significantly. These findings suggest that LRPPRC plays a role in inhibiting the expression of lipoic acid and copper chaperone proteins during Elesclomol-induced copper death in ovarian cancer. This inhibition collectively diminishes the expression and activity changes in complex IV, induces mitochondrial dysfunction, and promotes cuproptosis in ovarian cancer. This study further demonstrates that inhibiting the oxidative phosphorylation complex IV can enhance copper-induced cell death in ovarian cancer. Full article

Astrocytes and microglia constitute nearly half of all central nervous system cells and are indispensable for its proper function. Both exhibit striking morphological and functional heterogeneity, adopting either neuroprotective (A2, M2) or proinflammatory (A1, M1) phenotypes in response to cytokines, pathogen-associated molecular patterns (PAMPs)/damage-associated molecular patterns (DAMPs), toll-like receptor 4 (TLR4) activation, and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling. Crucially, many of these phenotypic transitions arise during the earliest stages of neurodegeneration, when glial dysfunction precedes overt neuronal loss and may act as a primary driver of disease onset. This review critically examines glial-centered hypotheses of neurodegeneration, with emphasis on their roles in early disease phases: (i) microglial polarization from an M2 neuroprotective state to an M1 proinflammatory state; (ii) NLRP3 inflammasome assembly via P2X purinergic receptor 7 (P2X7R)-mediated K⁺ efflux; (iii) a self-amplifying astrocyte–microglia–neuron inflammatory feedback loop; (iv) impaired microglial phagocytosis and extracellular-vesicle–mediated propagation of β-amyloid (Aβ) and tau; (v) astrocytic scar formation driven by aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP)/vimentin, connexins, and janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling; (vi) cellular reprogramming of astrocytes and NG2 glia into functional neurons; and (vii) mitochondrial dysfunction in glia, including Dynamin-related protein 1/Mitochondrial fission protein 1 (Drp1/Fis1) fission imbalance and dysregulation of the sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Sirt1/PGC-1α) axis. Promising therapeutic strategies target pattern-recognition receptors (TLR4, NLRP3/caspase-1), cytokine modulators (interleukin-4 (IL-4), interleukin-10 (IL-10)), signaling cascades (JAK2–STAT, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphoinositide 3-kinase–protein kinase B (PI3K–AKT), adenosine monophosphate-activated protein kinase (AMPK)), microglial receptors (triggering receptor expressed on myeloid cells 2 (TREM2)/spleen tyrosine kinase (SYK)/ DNAX-activating protein 10 (DAP10), siglec-3 (CD33), chemokine C-X3-C motif ligand 1/ CX3C motif chemokine receptor 1 (CX3CL1/CX3CR1), Cluster of Differentiation 200/ Cluster of Differentiation 200 receptor 1 (CD200/CD200R), P2X7R), and mitochondrial biogenesis pathways, with a focus on normalizing glial phenotypes rather than simply suppressing pathology. Interventions that restore neuroglial homeostasis at the earliest stages of disease may hold the greatest potential to delay or prevent progression. Given the complexity of glial phenotypes and molecular isoform diversity, a comprehensive, multitargeted approach is essential for mitigating Alzheimer’s disease and related neurodegenerative disorders. This review not only synthesizes pathogenesis but also highlights therapeutic opportunities, offering what we believe to be the first concise overview of the principal hypotheses implicating glial cells in neurodegeneration. Rather than focusing on isolated mechanisms, our goal is a holistic perspective—integrating diverse glial processes to enable comparison across interconnected pathological conditions. Full article

Microproteins are small polypeptides translated from short open reading frames (sORFs) that typically encode < 100 amino acids. Advances in ribosome profiling, mass spectrometry, and computational prediction have revealed a growing number of microproteins that play important roles in cellular metabolism, organelle function, and stress adaptation; however, these were considered non-coding or functionally insignificant. At the mitochondrial level, microproteins, such as MTLN (also known as mitoregulin/MOXI) and BRAWNIN, contribute to lipid oxidation, oxidative phosphorylation efficiency, and respiratory chain assembly. Other microproteins at the endoplasmic reticulum–mitochondria interface, including PIGBOS and several muscle-resident regulators of calcium cycling, show diverse biological contexts in which these microproteins act. A subset of microproteins responds to nutrient availability. For example, SMIM26 modulates mitochondrial complex I translation under serine limitation, and non-coding RNA expressed in mesoderm-inducing cells encoded with peptides facilitates glucose uptake during differentiation, indicating that some microproteins can affect metabolic adaptation through localized translational- or organelle-level mechanisms. Rather than functioning as primary nutrient sensors, these microproteins complement classical nutrient-responsive pathways such as AMP-activated protein kinase-, peroxisome proliferator-activated receptor-, and carbohydrate response element binding protein-mediated signaling. As the catalog of microproteins continues to expand, integrating proteogenomics, nutrient biology, and functional studies will be central to defining their physiological relevance; these integrative approaches will also help reveal their potential applications in metabolic health. Full article

Callicarpa americana L. is a member of the Lamiaceae family with important ornamental and medicinal value. Although the chloroplast genome of Lamiaceae has been extensively studied, its mitochondrial genome remains unreported, limiting a comprehensive understanding of the phylogeny and genome evolution of Lamiaceae. In this study, the complete mitochondrial genome of C. americana was successfully assembled for the first time. The genome is 499,565 bp in length, showing a complex multi-branched closed-loop structure that contains 37 protein-coding genes, 23 tRNA genes, and 4 rRNA genes. The difference in mitochondrial genome size is relatively large compared to Orobanchaceae species, but the difference in GC content is not obvious. The expansion of genome size was mainly due to the accumulation of non-coding regions and repetitive sequences. Meanwhile, two pairs of long repetitive sequences (LR3 and LR5) mediated homologous recombination. The mitogenome was also identified; there were a total of 494 C-to-U RNA editing sites in protein-coding genes. In addition, 42 mitochondrial plastid DNA fragments (MTPTs) were detected, with a total length of 21,464 bp, accounting for 4.30% of the genome. Repeat sequence analysis showed that tetranucleotide SSR was the most abundant repeat type in the mitochondria of Lamiaceae. Phylogenetic analysis based on the alignment of 32 protein-coding gene sequences showed that Callicarpa is sister to the other eight species of Lamiaceae. This work fills an important gap by presenting the first complete mitochondrial genome of C. americana, providing an important data resource for further understanding the structural evolution, dynamic recombination mechanism, and phylogeny of the mitochondrial genome of Lamiaceae. Full article