Cell Metabolism
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2022
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IF 31.373
Xie Li,Yinan Zhang,Lingyan Xu,Aoxue Wang,Yejun Zou,Ting Li,Li Huang,Weicai Chen,Shuning Liu,Kun Jiang,Xiuze Zhang,Dongmei Wang,Lijuan Zhang,Zhuo Zhang,Zeyi Zhang,Xianjun Chen,Wei Jia,Aihua Zhao,Xinfeng Yan,Haimeng Zhou,Linyong Zhu,Xinran Ma,Zhenyu Ju,Weiping Jia,Congrong Wang,Joseph Loscalzo,Yi Yang,Yuzheng Zhao
Summary Despite its central importance in cellular metabolism, many details remain to be determined regarding subcellular lactate metabolism and its regulation in physiology and disease, as there is sensitive spatiotemporal resolution of lactate distribution, and dynamics remains a technical challenge. Here, we develop and characterize an ultrasensitive, highly responsive, ratiometric lactate sensor, named FiLa, enabling the monitoring of subtle lactate fluctuations in living cells and animals. Utilizing FiLa, we demonstrate that lactate is highly enriched in mammalian mitochondria and compile an atlas of subcellular lactate metabolism that reveals lactate as a key hub sensing various metabolic activities. In addition, FiLa sensors also enable direct imaging of elevated lactate levels in diabetic mice and facilitate the establishment of a simple, rapid, and sensitive lactate assay for point-of-care clinical screening. Thus, FiLa sensors provide powerful, broadly applicable tools for defining the spatiotemporal landscape of lactate metabolism in health and disease.
研究领域:
细胞生物学
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代谢
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生物医学工程
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疾病模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
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IF 6.7
Yali Yang,Jie Jiang,Jing He,Yun Ju,Yanxiao Jiang,Hong Zhang
Inherited metabolic diseases (IMDs) have drawn considerable attention due to their disruption of normal metabolic pathways. However, conventional extraction techniques are predominantly offline and time-consuming, making them inadequate for the rapid screening required in clinical settings. We developed a novel method involving the extraction of dried sample spots, which are subsequently mixed with charged water (H2O) before infusion electrospray ionization-mass spectrometry analysis. This method was successfully applied for the simultaneous determination of nine amino acid and seven acylcarnitine indicators in dried serum, blood, and urine spots, covering the majority of IMDs routinely screened in hospitals. Compared with conventional approaches, the sensitivity of the new technique improved by nearly threefold, and in some cases, by up to an order of magnitude. The method’s clinical applicability was further confirmed through comparison with the recommended liquid chromatography-tandem mass spectrometry platform and was evaluated using serum samples from three healthy individuals. Additionally, the effect of charged H2O was investigated in detail. A potential mechanism was proposed, suggesting that positively charged H2O enhances ionization by repelling inorganic salts and increasing the density of charges around the target analytes. Although the high surface tension of H2O can, to some extent, suppress ionization, the incorporation of charged H2O in this workflow boosted analytical sensitivity. Overall, this study introduces a simple, rapid, and highly efficient method for the clinical screening of amino acid and acylcarnitine-related IMDs, offering a promising alternative to conventional techniques.
研究领域:
临床化学
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质谱技术
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代谢紊乱疾病
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分析化学
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医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）