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Main Authors: Ao, Jianpeng, Yin, Jiaze, Lin, Haonan, Ding, Guangrui, Guan, Youchen, Weinberg, Bethany, Dong, Dashan, Xia, Qing, Guo, Zhongyue, Savini, Marzia, Gao, Biwen, Cheng, Ji-Xin, Wang, Meng C.
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2504.04305
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author Ao, Jianpeng
Yin, Jiaze
Lin, Haonan
Ding, Guangrui
Guan, Youchen
Weinberg, Bethany
Dong, Dashan
Xia, Qing
Guo, Zhongyue
Savini, Marzia
Gao, Biwen
Cheng, Ji-Xin
Wang, Meng C.
author_facet Ao, Jianpeng
Yin, Jiaze
Lin, Haonan
Ding, Guangrui
Guan, Youchen
Weinberg, Bethany
Dong, Dashan
Xia, Qing
Guo, Zhongyue
Savini, Marzia
Gao, Biwen
Cheng, Ji-Xin
Wang, Meng C.
contents 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 significance of lysosomal metabolism, a method for its in vivo measurement is currently lacking. Here, we report optical boxcar-enhanced, fluorescence-detected mid-infrared photothermal microscopy, together with AI-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. Additionally, 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.
format Preprint
id arxiv_https___arxiv_org_abs_2504_04305
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle FILM: Mapping organellar metabolism by mid-infrared photothermal modulated fluorescence
Ao, Jianpeng
Yin, Jiaze
Lin, Haonan
Ding, Guangrui
Guan, Youchen
Weinberg, Bethany
Dong, Dashan
Xia, Qing
Guo, Zhongyue
Savini, Marzia
Gao, Biwen
Cheng, Ji-Xin
Wang, Meng C.
Biological Physics
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 significance of lysosomal metabolism, a method for its in vivo measurement is currently lacking. Here, we report optical boxcar-enhanced, fluorescence-detected mid-infrared photothermal microscopy, together with AI-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. Additionally, 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.
title FILM: Mapping organellar metabolism by mid-infrared photothermal modulated fluorescence
topic Biological Physics
url https://arxiv.org/abs/2504.04305