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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

KAT8-mediated MDH2 lactylation promotes renal cancer progression by enhancing mitochondrial function and stress resistance

Yuangui Tang,Chenyun Dai,Huihui Yang,Xian Yang,Ziyu Chen,Jinxiu Dou,Liuxu Zhang,Tao Bai,Junfang Zheng

Non-histone proteins localized in membrane, cytosol and nucleus are lactylated to promote tumor progression. However, whether mitochondrial proteins undergo lactylation and contribute to tumor progression remains unexplored. Here, we identified multiple lactylated mitochondrial proteins in human renal cell carcinoma (RCC) cells using lactylome profiling. Among these, malate dehydrogenase 2 (MDH2)–the only lactylated protein in the tricarboxylic acid (TCA) cycle–emerged as a key target, with K239 as its lactylation site. MDH2 K239la levels are regulated by KAT8 and SIRT3. Under low-glucose, high-lactate conditions mimicking the tumor microenvironment, MDH2 K239la elevated the NADH/NAD + ratio to drive ATP production and boosted NADPH generation to reduce ROS. This enables cells to alleviate oxidative stress, sustain mitochondrial function, and promote RCC malignancy in vitro and in vivo . Mechanistically, MDH2 K239la enhances MDH2 enzymatic activity and strengthens its interaction with the citrate transporter SLC25A1. This facilitates citrate efflux, fueling IDH1-dependent NADPH production when lactate serves as an energy source. Collectively, we unveil a lactylation-dependent mechanism that reprograms mitochondrial metabolism to confer oxidative stress resistance and drive RCC progression. Targeting mitochondrial proteins lactylation, exemplified by MDH2 K239la , represents a promising therapeutic strategy for RCC.

CAS / MDL: 107-95-9
研究领域: 癌症生物学 · 生物化学 · 细胞生物学 · 分子生物学 · 代谢工程 · 肿瘤学
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FOOD CHEMISTRY · 2024 · IF 8.5

Autophagy-mediated energy charge sustainability alleviated postharvest quality deterioration of strawberry (Fragaria × ananassa)

Yicheng Ren,Quan Ma,Dong Li,Yanpei Chen,Qinyang Cheng,Zisheng Luo

Fluctuations in energy status are critical physiological factors influencing postharvest fruit quality. However, the role of autophagy, a stress-resistant biological process, in regulating postharvest fruit energy status remains unclear. In this study, we treated strawberry fruit with the autophagy inhibitor hydroxychloroquine (HCQ) to investigate the role of autophagy in maintaining energy status. The results demonstrated that HCQ treatment inhibited autophagosome formation, reducing relative autophagic activity by 73 % on day 6. HCQ treatment also reduced the energy charge and the NADH/NAD + ratio by 5 % and 61 %, respectively, on day 2. Corresponding to the decline in energy status, HCQ treatment led to a reduction in cytochrome C oxidase (CCO) and succinate dehydrogenase (SDH) activities by 47.48 % and 56.34 %, respectively, on day 3. Additionally, fluctuations in energy charge led to abnormalities in ripening and decreased stress resistance in autophagy-inhibited fruit. In conclusion, this study provides evidence that autophagy-mediated energy charge sustainability mitigates postharvest quality deterioration in fruit.

研究领域: 植物生理学 · 采后生物学 · 分子生物学
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BIORESOURCE TECHNOLOGY · 2022 · IF 11.889

The enhancement on biohydrogen production by the driving forces from extracellular iron oxide respiration

Lei Yu,Wei-xin Cheng,Quan Wang

Biohydrogen productions from xylose and glucose under dark condition were enhanced by the presence of natural Fe 3 O 4 . The electron equivalent of H 2 fractions accounted for 4.55 % and 5.69 % of the total given xylose and glucose in the experiments without Fe 3 O 4 , and that were correspondingly increased to 5.14 % and 6.50 % in the experiments with 100 mg/L of Fe 3 O 4 , respectively. Moreover, Fe 3 O 4 increased the total intracellular NAD(H) concentrations by 8.84 % and 8.37 %, and boosted the ratios of NADH/NAD + by 8.33 % and 17.72 % in xylose and glucose fermentation, respectively, comparing to the corresponding control experiments. The formation of electron couples of Fe(III)/Fe(II) during the iron oxide respiration and more generation of active extracellular polymeric substances components were determined as the important reasons for the improved biohydrogen production performance. Thus, a promotion mechanism of the internal “driving forces” from extracellular iron oxide respiration on the biohydrogen production was proposed.

CAS / MDL: 1317-61-9
研究领域: 生物技术 · 环境工程 · 微生物学
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SHOCK · 2024 · IF 2.7

D4-Chip Reveals Impaired T Cell Function in Sepsis: Insights from Plasma Microenvironment Analysis and Mitochondrial Targeted Therapy

Liu Lijuan,Wang Ruoyu,Pu Xuexue,Zha Yutao,Yang Xiao,Fang Xiao,Liu Yong,Shao Min,Zhu Ling,Ren Xiaoou,Deng Guoqing,Yang Ke

Background Sepsis, a systemic inflammation syndrome initiated by infection, poses significant challenges due to its intricate pathophysiology. T cells play a crucial role in combating infections during sepsis. Despite previous observations indicating T cell dysfunction in sepsis, reliable in-vitro detection methods were lacking, and the factors influencing these impairments remained unclear. Methods We developed a novel method using the D 4 -Chip to assess sepsis T cell migration function. This microfluidic platform enabled precise analysis of migration function under controlled conditions. Additionally, We explored the impact of the plasma microenvironment on T cell behavior, along with the redox environment in sepsis, and assessed the potential efficacy of Mitoquinone mesylate (MitoQ), a mitochondrial-targeted drug. Results Our findings revealed impaired migration function in sepsis T cells compared to healthy controls. Interestingly, sepsis plasma enhanced the migration of healthy T cells, yet incubation with healthy plasma did not fully restore migration impairments in sepsis T cells. Subsequent investigations uncovered a significant increase in NADH/NAD+ levels in sepsis T cells, with healthy T cells exposed to various sepsis plasma conditions also showing elevated NADH/NAD+ levels. Importantly, MitoQ normalized abnormal intracellular NADH/NAD+ levels and enhanced the migration ability of T cells. Conclusions Short-term incubation with sepsis plasma does not directly inhibit T cell migration but instead affects T cell function by disrupting the intracellular redox environment. Improving the intracellular redox environment of sepsis patients contributes to restoring impaired migration and proliferation, with MitoQ demonstrating therapeutic potential.

研究领域: 免疫学 · 传染病学 · 药理学 · 细胞生物学
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RSC Advances · 2013 ·Vol. 3 ·期 44 ·21848-21855 · IF 2.562

Application of low frequency ultrasound to stimulate the bio-activity of activated sludge for use as an inoculum in enhanced hydrogen production

Wan-Qian Guo,Shan-Shan Yang,Ji-Wei Pang,Jie Ding,Xian-Jiao Zhou,Xiao-Chi Feng,He-Shan Zheng,Nan-Qi Ren

In order to increase hydrogen yield and shorten the lag time, low frequency ultrasonic (LFU) pretreatment was applied to stimulate the bio-activity of the seed bacteria, using waste activated sludge as the inoculum. A pretreated, sterilized sludge sample was seeded as the substrate for bio-hydrogen production. A Unisense microsensor multimeter with a hydrogen microelectrode was employed to examine the hydrogenase activities at different ultrasonic densities and exposure times. The optimum conditions were achieved at an ultrasonic density of 125 W L−1 and a reaction time of 10 s. A maximum hydrogen yield of 13.03 mL H2/g TS was obtained by LFU pretreatment under these optimal conditions, which was 18% higher than that obtained when seeding the raw sludge sample. To gain a better understanding of the end product distribution, three-dimensional excitation–emission matrix (3D-EEM) fluorescence spectroscopy was performed to characterize the dissolved organic matter (DOM) and extracellular polymeric substances (EPS) in the sludge samples during the anaerobic fermentation process. Hydrogen production from NADH/NAD+ conversion was also proved by EEM.

研究领域: 环境工程 · 生物技术 · 微生物学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

Enhancing photocatalytic hydrogen production from engineered Escherichia coli-biohybrid system via intracellular electron redirection

Song Lin,Zhengyu Tao,Zhenhui Li,Shangsong Li,Xiaoliang Wang,Xiaoman Liu,Xin Huang

The development of biotic-abiotic photosynthetic systems is becoming one of the most promising strategies towards the thirsty demand for sustainable energy production. However, considerable efforts are still required to further optimize the design and avoid the utilization of high-value substances while achieving highly efficient hydrogen production. Here we show a way to construct an Escherichia coli ( E. coli )-quantum dots hybrid system by expressing ferredoxin (Fd), Fd-NAD(P) + reductase (FNR), and [FeFe]-hydrogenase ([FeFe]H 2 ase) as a potential biocatalyst. We reveal that electrons originating from the quantum dots could be redirected through the newly established electron transport chain NADH/NAD + -FNR-Fd to [FeFe]H 2 ase, which contributes a key mechanism to boost the highest H 2 production activity (3149.5 μmol g dcw −1 h −1 ) by only using glycerol as the carbon source. Our work sheds light on the advantages of an intracellular biological hybrid system by combining the photocatalytic capacity with the optimized metabolic power to produce biofuels.

研究领域: 生物技术 · 生物能源 · 光合作用 · 催化
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SCIENCE OF THE TOTAL ENVIRONMENT · 2019 · IF 5.589

Enhanced denitrification performance of Alcaligenes sp. TB by Pd stimulating to produce membrane adaptation mechanism coupled with nanoscale zero-valent iron

Zeyu Wang,Cong Chen,Huan Liu,Dzmitry Hrynshpan,Tatsiana Savitskaya,Jianmeng Chen,Jun Chen

The microbial reduction of nitrate in the presence of nanoscale zero-valent iron (nZVI) was evaluated to assess the feasibility of employing nZVI for biological denitrification treatment. The effect of modified nZVI on the growth, metabolism, and denitrification performance of Alcaligenes sp. TB under aerobic conditions was studied. Results showed that Alcaligenes sp. TB with nZVI/Pd had 31.5% increase in nitrate removal and 18.1% decrease in nitrite accumulation within 28 h. nZVI/Pd exhibited less inhibition on the cell growth (OD 600  = 0.725), NADH/NAD + ratio (86% of control), and electron transfer system activity (68.5% of control). In addition, nZVI/Pd decreased the membrane fluidity by increasing the trans/cis isomerization ratio (317.7% of control) to enhance the resistance of nZVI. This study underlines the effects of nZVI/Pd on membrane susceptibility via membrane fatty acid transformation during denitrification and suggests the influence of engineered nanomaterials on denitrification.

研究领域: 环境微生物学 · 生物技术 · 水处理
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CHEMOSPHERE · 2022 · IF 8.943

Bio-Pd(0) diverting electron from CoQ-long chain to FDH/Hase-short chain during sulfamethoxazole degradation

Jinghao Wang,Huimin Liu,Song Song,Yuancai Chen,Yongyou Hu

Microbial electron output capacity is critical for organic contaminants biodegradation. Herein, original C. freundii JH could oxidate formate in anaerobic respiration, but lack the ability to degrade sulfamethoxazole (SMX). While the incorporation of Pd(0) could effectively improve the electron output via improving the combination between flavins and c-type cytochromes (c-Cyts), increasing the activities of key enzymes (formate dehydrogenase , hydrogenase, F 0 F 1 -ATPases), etc. More importantly, the presence of Pd(0) caused the NADH dehydrogenase (complex I) nearly in idle, and triggered the decrease of NADH/NAD + ratio and increase of H + -efflux transmembrane gradient, eventually resulting in the electrons diverting from CoQ-involved long respiratory chain (decreasing from 91.67% to 36.25%) to FDH/Hases-based hydrogen-producing short chain (increasing from 22.44% to 84.88%), which further intensified the electron output. Above changes effectively launched and guaranteed the high-level SMX degradation by palladized C. freundii JH, alleviating the ecotoxicity of SMX in aquatic and terrestrial environments. These conclusions provided the new view to regulate the microbial electron output behaviors.

CAS / MDL: 13820-53-6 723-46-6
研究领域: 环境微生物学 · 生物修复 · 电子传递 · 环境毒理学
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CHEMICAL ENGINEERING JOURNAL · 2020 · IF 10.652

Improving hydrogen and methane co-generation in cascading dark fermentation and anaerobic digestion: The effect of magnetite nanoparticles on microbial electron transfer and syntrophism

Jun Cheng,Hui Li,Lingkan Ding,Junhu Zhou,Wenlu Song,Yu-You Li,Richen Lin

The efficiency of microbial electron transfer is fundamental for determining the performance of fermentative hydrogen/methane production. To facilitate microbial electron transfer, conductive magnetite nanoparticles (MNPs) were added into a cascading dark fermentation and anaerobic digestion system that was inoculated with Enterobacter aerogenes ZJU1 and methanogenic activated sludge (MAS), respectively. During the hydrogen-producing stage, the ratio of NADH/NAD + and the activities of hydrogenase and electron transport system (ETS) of E. aerogenes ZJU1 were all increased by dosing 200 mg/L MNPs, which was conducive to hydrogen production through the NADH-dependent pathway. In the presence of 200 mg/L MNPs, hydrogen production increased by 21.1%, while subsequent methane production improved by 22.9%. Electrochemical analysis demonstrated the improvement in extracellular electron transfer capacity of MAS after adding MNPs, which can be ascribed to the contribution of MNPs and electrochemically active extracellular polymeric substances (EPS) induced by MNPs, such as humic acid-like and fulvic acid-like substances. Bacteria Syntrophomonas and Archaea Methanosarcina were the dominating enriched syntrophic partners, and the expression of functional genes involved in CO 2 reduction to methane pathway was found to increase. Therefore, a more efficient fermentative hydrogen and methane co-production system was established by improving microbial electron transfer with the addition of MNPs.

CAS / MDL: 1317-61-9
研究领域: 环境工程 · 微生物学 · 生物技术 · 生物能源
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