Succinate Dehydrogenase Research Articles

Photosynthetic bacteria (PSB) are protein-rich and a high-quality producer of microbial proteins. In this study, PSB were cultivated using self-fermented kitchen waste fermentation broth under controlled light intensity and light cycle conditions. Biomass and protein concentrations were measured daily, and microbial community composition and functional succession were analyzed using high-throughput sequencing and bioinformatic tools to investigate the effects of photoperiod on PSB growth and protein synthesis. The results showed that PSB had the highest biomass and protein production of 1356.5mg/L and 564.3mg/L at 4000lx and 24h light/0h dark, respectively. Organic pollutant removal was also the highest, with 89.7% chemical oxygen demand (COD) removal and 65.8% ammonia nitrogen removal. Microbiological analysis indicated that the selected light intensity and light/dark cycles were highly favorable for PSB growth. Under these conditions, the dominance of Rhodopseudomonas was further strengthened. During the cultivation process, PSB adjusted its metabolic pathway and shifted its metabolic focus from carbon metabolism to nitrogen metabolism. In addition, the activities of ribulose bisphosphate carboxylase (Rubisco), a key enzyme for photosynthesis, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and succinate dehydrogenase (SDH), key enzymes of the tricarboxylic acid (TCA) cycle, were enhanced in PSB. These findings provide an important reference for an in-depth understanding of the growth characteristics, metabolic responses, and protein biosynthesis of PSB in the treatment of kitchen waste fermentation broth.

A total of 45 l-menthol derivatives with thiosemicarbazide, semicarbazide, or thiazole structures were designed and synthesized, and the in vitro inhibitory activities were evaluated against seven plant pathogens. Some title compounds exhibited remarkable antifungal activities. Specifically, compound 4n demonstrated a significant antifungal effect against Sclerotinia sclerotiorum with an EC50 value of 1.03 mg/L, outperforming thifluzamide (1.32 mg/L). Furthermore, at a concentration of 200 mg/L, 4n displayed excellent protective (97.5%) and curative (95.7%) effects on S. sclerotiorum-infected carrots. In the phytotoxicity experiment, 4n exhibited no effect on the normal germination of carrot and mung bean seeds. Fluorescence imaging revealed a significant accumulation of reactive oxygen species (ROS) in mycelia treated with 4n. Additionally, 4n exhibited substantial inhibitory effects on the sclerotium formation and germination of S. sclerotiorum. A further mechanism study revealed that 4n could dose-dependently increase the cell membrane permeability and significantly inhibit the defense/respiration-related enzymes of S. sclerotiorum. The transcriptome analysis suggested that 4n could notably affect the gene expression related to the oxidation-reduction process and oxidoreductase activity. The enzyme inhibition assay and molecular docking studies implied that 4n could be a potential succinate dehydrogenase (SDH) inhibitor. These findings indicated that this class of l-menthol thiosemicarbazide derivatives holds promise as potential fungicides for the prevention and treatment of postharvest sclerotinia rot.

Clothianidin, a widely used neonicotinoid pesticide, poses potential ecological risks to aquatic ecosystems due to its unique mode of action and widespread environmental dispersal. This study investigates the toxic effects of clothianidin on Penaeus vannamei at different concentrations over 28 days. High concentrations of clothianidin significantly affected shrimp physiology, as evidenced by changes in survival rate and weight gain. Markers of oxidative stress, including decreased respiratory burst, reduced glutathione levels, and diminished antioxidant enzyme activities, indicated that clothianidin triggered oxidative stress responses in shrimp. Additionally, changes in lactate dehydrogenase, succinate dehydrogenase, and isocitrate dehydrogenase activities suggested disruptions in energy metabolism in the hepatopancreas. Analysis of the nervous system revealed significant disturbances in neural signaling, reflected by altered levels of acetylcholine, acetylcholinesterase, and dopamine. Transcriptomic analysis highlighted significant changes in gene expression and metabolic processes in the nervous system. This study demonstrates that clothianidin disrupts oxidative balance, energy metabolism, and neural signaling, affecting the growth of P. vannamei and providing valuable insights into its biochemical and transcriptomic toxicity in aquatic environments.Graphic Supplementary InformationThe online version contains supplementary material available at 10.1007/s44154-025-00259-0.

Butylidenephthalide (NBP), an active compound derived from Ligusticum chuanxiong essential oil, exhibits potent antifungal activity against Sclerotium rolfsii, a destructive plant pathogen that causes stem rot in peanuts. However, the target protein of NBP in S. rolfsii is unclear. This study elucidates that NBP mainly inhibits the glyoxylate cycle and pyruvate metabolism and also promotes ROS accumulation by affecting the activities of catalase (CAT) and superoxide dismutase (SOD) in the mycelium, thereby inhibiting the mycelial growth of S. rolfsii. The isocitrate lyase (SrICL) was identified as a potential target protein of NBP using drug affinity responsive target stability (DARTS) combined with transcriptomics and metabolomics. NBP significantly inhibited the SrICL activity, disrupted the succinate dehydrogenase (SDH) function, and inhibited energy metabolism, ultimately resulting in the inhibition of fungal growth. Furthermore, deletion of FgICL led to a significantly decreased sensitivity to NBP in Fusarium graminearum, which indicated that ICL might be a potential target of NBP. These findings demonstrate NBP's potential as an ecofriendly fungicide with a novel mode of action.

The central link in the cell's energy metabolism are the substrates and enzymes of the Krebs cycle, as well as the electron transport chain of the mitochondria. Metabolites of the Krebs cycle are also present in the bloodstream and perform important functions outside the cycle. The aim of this review is to establish new concepts on the mechanisms of action of succinate in stress situations, taking into account the mechanism of substrate phosphorylation.To study scientific achievements in the field of energy metabolism, such methods as system-structural and comparative were used. The use of the designated methods allowed us to present the author's scheme, displaying the general patterns of metabolic changes in succinate during hypoxia, inflammation and tumor growth.Molecular mechanisms of succinate action associated with the development of pathological conditions have been identified. The features of the action of the enzyme succinate dehydrogenase are considered. It has been established that energy-dependent processes dominate in maintaining the main functional systems of the body. Potential molecular markers that reflect real value in monitoring the dynamics of the pathological process have been identified.A conclusion is formulated about the need for further study of the role of succinate in cellular energy homeostasis for both fundamental science and clinical medicine.

Background This study aimed to investigate the impact of magnoflorine (Mag) on acute exercise-induced fatigue and its underlying mechanisms. Methods Seventy-two male Kunming mice were divided into six groups: a non-treatment control, a vehicle control (ddH2O), a positive control (Gaoshan Hongjingtian Koufuye), and three Mag groups (10, 25, and 50 mg/kg). Antifatigue effects were assessed through organs and body weights, exercise endurance, and biochemical parameters, including superoxide dismutase (SOD), reactive oxygen species (ROS), malonydialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH), total antioxidant capacity (T-AOC), glycogen, succinate dehydrogenase (SDH), malate dehydrogenase (MDH), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and liver tissue histochemistry. Activation of the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) signaling pathway was evaluated using Western blot. Results No significant differences were observed in organs and body weights, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and liver cellular structures. Mag significantly prolonged exercise endurance in Rota-rod and forced swimming tests compared to controls. Mag increased hemoglobin (Hb), testosterone/corticosterone (T/C), and creatine kinase (CK) levels and decreased serum lactic acid (LD), lactate dehydrogenase (LDH), and blood urea nitrogen (BUN). Mag also enhanced glycogen storage, SDH, and MDH levels. Mechanistically, Mag exhibits antioxidant and anti-inflammatory properties in liver tissues and hepatocytes via activation of the PI3K/AKT signaling pathway. Conclusion Mag alleviated acute exercise-induced fatigue by modulating energy metabolism, antioxidation, and anti-inflammation through the PI3K/AKT signaling pathway. These findings suggest potential therapeutic implications for Mag in combating exercise-induced fatigue and related physiological stressors.

Role of nitric oxide in mitochondrial energetics and stress/ease-responsive neuroendocrine receptor expression in developing zebrafish larvae.

Development of succinate dehydrogenase subunit B-deficient tumor models for preclinical immunotherapy testing.

The relationship between mitochondrial respiration metabolism, energy efficiency and ultraweak luminescence in strawberry fruit.

Obeticholic acid does not restore Western diet-induced alterations in hepatic mitochondrial respiration.

Risk assessment and underlying mechanisms of pydiflumetofen resistance in Alternaria tenuissima and Alternaria alternata.

The liver and skeletal muscle are metabolically interconnected organs vital for maintaining systemic homeostasis. Arsenic toxicity is known to adversely affect both organs individually, yet the mechanistic link between arsenic-induced liver dysfunction and skeletal muscle deterioration remains unclear. This study aimed to investigate whether arsenic-induced alterations in hepatic metabolism are associated with changes in skeletal muscle health. BALB/c mice were divided into four groups: Control, 0.2ppm arsenic, 2ppm arsenic, and 20ppm arsenic. For 30days, sodium arsenite was administered in the drinking water ad libitum. Arsenic exposure led to elevated serum ALT and AST levels, increased hepatic lipid accumulation, and dysregulated the expression of oxidative stress defense components (Nrf2/Keap1), lipid metabolism regulators (PPAR-γ and PPAR-α), β-oxidation and lipogenic enzymes (CPT-1, and SREBP-1), as well as hepatic energy sensors (p-mTOR and p-AMPK). These hepatic changes were accompanied by oxidative stress and elevated proinflammatory cytokines (TNF-α, IL-6) in the liver and serum. Concurrently, skeletal muscle exhibited functional decline, as evidenced by decreased grip strength and elevated serum creatine kinase levels. Histological and Succinate dehydrogenase (SDH) analysis further revealed atrophy, characterized by reduced fiber cross-sectional area and a fiber-type shift from fast-twitch (Type II) to slow-twitch (Type I) fibers respectively. At the molecular level, arsenic exposure upregulated the muscle-specific ubiquitin ligases MuRF1 and atrogin-1, accompanied by NF-κB activation, indicating increased proteolysis and inflammation. Additionally, decreased irisin expression in both liver and muscle and reduced serum insulin levels indicated systemic metabolic dysregulation. Correlation analysis of inflammatory markers with indices of liver and muscle injury, together with evidence of crosstalk between these tissues, revealed significant associations. Collectively, these findings suggest that arsenic-induced hepatic disturbances may indirectly contribute to skeletal muscle wasting via systemic inflammation, supporting the possible involvement of a liver-muscle axis in arsenic toxicity.

In this work, a series of novel β-ionone derivatives bearing an isoxazole hydrazide moiety were designed, synthesized, and evaluated for their antifungal activities. In vitro bioassay results indicated that most of the synthesized compounds exhibited significant antifungal activity against seven tested phytopathogenic fungi. Notably, compound D28, bearing a 3,4-difluorophenyl group, showed good broad-spectrum antifungal effects against Rhizoctonia solani, Valsa mali, Gibberella zeae, Altenaria solani, Botrytis cinerea, and Colletotrichum orbiculare, with EC50 (half-maximal effective concentration) values of 0.204, 0.586, 2.59, 1.87, 3.06, and 4.73 μg/mL, respectively. In vivo preventative effects of compound D28 against R. solani and V. mali revealed that it had potential as a novel antifungal agent. Mechanistic studies demonstrated that compound D28 exerted its antifungal activity against R. solani by disrupting mycelial morphology, increasing cell membrane permeability, inducing the production and accumulation of reactive oxygen species (ROS), and impairing mitochondrial function, ultimately leading to the inhibition of hyphal proliferation. Furthermore, compound D28 exhibited potent inhibitory activity against succinate dehydrogenase (SDH), with an IC50 value of 5.38 μg/mL. Binding mode analysis further elucidated its binding mode with SDH, which closely resembles that of the SDHI fungicide boscalid. The above-mentioned results indicated that β-ionone derivatives containing isoxazole hydrazide moiety have the potential as novel SDH inhibitors.

Undifferentiated pleomorphic sarcoma (UPS) remains one of the most clinically aggressive and poorly characterized soft-tissue sarcoma subtypes. To uncover distinctive molecular traits for UPS, a multiomics analysis of UPS compared with leiomyosarcoma (LMS) and liposarcoma (LPS) was performed. Transcriptomic profiling revealed that UPS exhibits overexpression of genes encoding succinate dehydrogenase (SDH) subunits, particularly SDHB, SDHC, and SDHD, distinguishing it from LMS and dedifferentiated LPS. This finding was validated using The Cancer Genome Atlas Sarcoma dataset. High SDHB expression in UPS was significantly associated with shorter overall survival, shorter recurrence-free survival, and shorter overall survival from the date of first metastasis. IHC validated elevated SDHB protein levels in UPS and LMS relative to dedifferentiated LPS. Despite overexpression of SDH subunits, metabolomic profiling demonstrated a significantly higher succinate-to-fumarate ratio in UPS, suggesting functional impairment of SDH enzymatic activity potentially due to posttranslational modifications, altered assembly of SDH subunits, or imbalanced tricarboxylic acid flux. This paradoxical phenotype of SDH overexpression with enzymatic dysfunction defines a unique molecular and metabolic subtype of UPS with prognostic significance. Recognition of this distinct SDH-associated molecular and metabolic phenotype provides insights into UPS pathogenesis, identifies a potential novel prognostic biomarker, and suggests a new avenue for metabolic-targeted therapy.Significance:This study identified a paradoxical phenotype of SDH subunit overexpression with functional impairment in UPS, defining a molecular/metabolic subtype associated with poor prognosis. It offers new data on UPS pathogenesis and treatment.

Background/Objectives: γ-aminobutyric acid (GABA), a non-protein amino, is synthesized from glutamic acid through the catalytic activity of glutamate decarboxylase (GAD). As a key signaling molecule, GABA plays a vital role in plant responses to abiotic stresses. To explore the potential involvement of the GABA gene family in Juglans regia’s response to environmental stressors, a comprehensive genome-wide identification and analysis of GABA-related genes was performed. Methods: The study examined their protein features, evolutionary relationships, chromosomal locations, and promoter cis-regulatory elements. Additionally, the expression patterns of GABA family genes were analyzed in J. regia seedlings subjected to salt and drought stress. Results: Genome analysis identified three main components of the GABA metabolic pathway in J. regia: glutamate decarboxylases (GADs), GABA transaminases (GABA-Ts), and succinic semialdehyde dehydrogenases (SSADHs). These genes were unevenly distributed across 14 chromosomes, with chromosome 10 containing the highest number. Promoter analysis revealed that about 80% of cis-acting elements were linked to plant hormone regulation, such as abscisic acid (ABA), and stress responses, including drought and high-salinity. Phylogenetic analysis showed that JrGAD1 was distantly related to other JrGAD members, while certain JrGABA-T and JrSSADH genes formed closely related pairs. Under salt and drought stress, JrSSADH23 expression was highly upregulated (2.60-fold and 2.24-fold, respectively), a trend observed for most JrSSADH genes. Conclusions: These findings offer valuable insights into the molecular basis of GABA metabolism in J. regia’s stress adaptation and identify promising genetic targets for developing stress-tolerant varieties.

Introduction Pheochromocytomas and paragangliomas (PPGLs) are associated with poor prognosis especially in patients with metastatic spread. This study aims to investigate the therapeutic potential of 131 I-MIBG and the PARP inhibitor fluzoparib monotherapies and their combination on two distinct PC12-derived stable cell lines: PC12-NET cells and PC12-NET-SDHB cells. Methods Lentiviral transduction was used to generate PC12-NET cells overexpressing the norepinephrine transporter (NET) and PC12-NET-SDHB cells with suppressed succinate dehydrogenase subunit B (SDHB) expression. The specificity of PC12-NET cells to the 131 I-MIBG was confirmed through desipramine inhibition assays. Subsequently, the synergistic effects of 131 I-MIBG and fluzoparib monotherapies and their combination were assessed in vitro through proliferation assays, cell cycle analysis and apoptosis analysis in both cell lines. Results NET overexpression significantly enhanced 131 I-MIBG uptake in PC12-NET cells, confirming NET expression as a critical determining of 131 I-MIBG therapeutic efficacy. The combination of 131 I-MIBG with fluzoparib exhibited substantial synergistic effects in PC12-NET cells, leading to a significant G2/M phase arrest and a marked increase in apoptosis compared to monotherapy, particularly where monotherapy alone was ineffective. Notably, although low expression of the SDHB did not alter cell proliferation in response to 131 I-MIBG treatment, PC12-NET-SDHB cells exhibited a greater sensitivity to fluzoparib-induced G2/M phase arrest than PC12-NET cells. Discussion The combined of 131 I-MIBG with PARP inhibitor demonstrated a synergistic antitumor effect in PC12-NET cells. While PC12-NET-SDHB cells display comparable sensitivity to 131 I-MIBG as PC12-NET cells, they exhibited heightened responsiveness to PARP inhibitor treatment.

Nerol induces mitochondrial apoptosis and autophagy in Botrytis cinerea and its protection on postharvest cherry tomato.

Succinate dehydrogenase inhibitors (SDHIs) are one of the major classes of phytofungicides that inhibit mitochondrial complex II and prevent mitochondrial respiration. Despite their broad applications, only a few SDHIs are available in the market, and rapidly evolving microbes demand the development of new fungicides. In this context, we designed thiazole-carboxamide analogues using structure-guided approaches. The antifungal screening afforded a few potential hits, 22a, with inhibition profiles superior to the comparable Boscalid and Fluxapyroxad across the tested fungi, with substantial selectivity toward Alternaria solani and Pyricularia oryzae. The active compound 22a (S2J-23-04) exhibited significant inhibition of SDH activity (IC50 = 20.01 μM), mycelium inhibition in A. solani (EC50 = 4.49 ± 1.04 μg/mL) and P. oryzae (EC50 = 5.13 ± 1.28 μg/mL), and in vivo activity against A. solani in tomatoes. A slight modification of 22a, i.e., replacing methyl with trifluoromethyl, afforded a superior analogue, 22k (S2J-23-47), with enhanced potency in fungal screening, SDH enzyme, and broad and equipotent mycelium inhibition verified by scanning electron microscopy (SEM). Thus, this study identified a potent selective antifungal lead molecule that can be optimized as a novel phytofungicide.

Metabolic defense mediated by ACOD1/itaconate is crucial for mammary epithelial cells to resist Streptococcus uberis infection.

Fusarium head blight (FHB), primarily caused by the Fusarium graminearum species complex (FGSC), reduces cereal yields and causes substantial economic losses globally. In China, Fusarium asiaticum is the predominant FGSC species, causing yield losses and deoxynivalenol contamination. Pydiflumetofen, a succinate dehydrogenase inhibitor, was widely used in China for FHB control. Among 5176 field isolates collected in 2023 from Hubei, Anhui, and Jiangsu provinces, five pydiflumetofen-resistant F. asiaticum isolates were identified. These isolates exhibited reduced sporulation and virulence. Site-directed mutagenesis confirmed that the FaSDHC2-A83V substitution conferred high resistance while impairing sporulation. No cross-resistance occurred with pyraclostrobin, phenamacril, or tebuconazole, but strong positive cross-resistance was observed with fluopyram and enpyracymid, and negative cross-resistance with benzovindiflupyr, a novel finding with potential implications for agricultural and clinical antifungal strategies. This study reports the first field-derived pydiflumetofen-resistant F. asiaticum mutants and identifies FaSDHC2-A83V as a key resistance marker, aiding monitoring and sustainable FHB management.