FILM: mapping organellar metabolism by mid-infrared photothermal-modulated fluorescence.

IF 32.1 1区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Nature Methods Pub Date : 2026-05-07 DOI:10.1038/s41592-026-03090-1

Jianpeng Ao, Jiaze Yin, Haonan Lin, Guangrui Ding, Youchen Guan, Marzia Savini, Bethany Weinberg, Dashan Dong, Qing Xia, Zhongyue Guo, Bowen Liu, Biwen Gao, Ji-Xin Cheng, Meng C Wang

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引用次数: 0

Abstract

Metabolism unfolds within specific organelles in eukaryotic cells. Lysosomes are highly metabolically active organelles, and their metabolic states dynamically influence signal transduction, cellular homeostasis and organismal physiopathology. Despite the importance of lysosomal metabolism, a method for its in vivo measurement is currently lacking. Here we report a fluorescence-detected mid-infrared photothermal microscope (FILM) implemented with optical boxcar demodulation, artificial intelligence-assisted data denoising and spectral deconvolution, to map metabolic activity and composition of individual lysosomes in living cells and organisms. Using this method, we uncovered lipolysis and proteolysis heterogeneity across lysosomes within the same cell, as well as early-onset lysosomal dysfunction during organismal aging. In addition, we discovered organelle-level metabolic changes associated with diverse lysosomal storage diseases. This method holds the broad potential to profile metabolic fingerprints of individual organelles within their native context and quantitatively assess their dynamic changes under different physiological and pathological conditions, providing a high-resolution chemical cellular atlas.

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胶片：利用中红外光热调制荧光绘制细胞器代谢图谱。

在真核细胞中，代谢在特定的细胞器内展开。溶酶体是高度代谢活跃的细胞器，其代谢状态动态影响信号转导、细胞稳态和机体生理病理。尽管溶酶体代谢很重要，但目前缺乏一种体内测量方法。在这里，我们报告了一种荧光检测的中红外光热显微镜（FILM），该显微镜采用光学箱车解调，人工智能辅助数据去噪和光谱反褶积，以绘制活细胞和生物体中单个溶酶体的代谢活性和组成。利用这种方法，我们发现了同一细胞内溶酶体的脂解和蛋白解异质性，以及机体衰老过程中溶酶体的早发性功能障碍。此外，我们发现细胞器水平的代谢变化与多种溶酶体贮积病相关。该方法具有广泛的潜力，可以分析单个细胞器在其天然环境中的代谢指纹，并定量评估其在不同生理和病理条件下的动态变化，提供高分辨率的化学细胞图谱。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Methods 生物-生化研究方法

CiteScore

58.70

自引率

1.70%

发文量

326

审稿时长

1 months

期刊介绍： Nature Methods is a monthly journal that focuses on publishing innovative methods and substantial enhancements to fundamental life sciences research techniques. Geared towards a diverse, interdisciplinary readership of researchers in academia and industry engaged in laboratory work, the journal offers new tools for research and emphasizes the immediate practical significance of the featured work. It publishes primary research papers and reviews recent technical and methodological advancements, with a particular interest in primary methods papers relevant to the biological and biomedical sciences. This includes methods rooted in chemistry with practical applications for studying biological problems.