Researchers perform metabolomic profiling of individual enlarged lysosomes

The research team led by Prof. XIONG Wei and Prof. CANG Chunlei from Life Science and Medicine of University of Science and Technology of China, realized lysosome typing based on single lysosome metabonomic information for the first time by stablishing a single lysosome metabonomic mass spectrometry detection technology. A deeply explore to the heterogeneity changes of lysosome metabonomics in the process of cellular senescence has been achieved. The result was published on Nature Methods.

Lysosomes are organelles present in almost all eukaryotic cells. Lysosomes are essential for maintaining energy and metabolic homeostasis, signal transduction, and recovery of damaged proteins and organelles. Previous reports indicate that cellular senescence is closely related to lysosomes and their internal metabolic processes.

There exists variety of lysosomes in a single cell, such as autophagy lysosome, endolysosome and so on. Studying the specificity of different types of lysosomes in the process of aging can provide new possibilities and research approaches for targeted development of drug targets for anti-aging and treatment of aging related diseases. Due to technical limitations, it is not possible to detect single lysosome metabonomics, let alone study cell aging from the perspective of single lysosome metabonomics.

Faced with this, the research group established the first single lysosomal mass spectrometry platform. The platform is based on single lysosome patch clamp combined with ultra-low speed induction electrospray ionization mass spectrometry. It realized the detection of metabolites directly without any pretreatment in cells, and more accurately retained the information of metabolites in lysosomes.

Through the technology platform, the research group conducted in-depth research on the metabolic heterogeneity of various types of lysosomes in the process of cell aging. Based on the single lysosome metabonomics, lysosomes from at least four cell sources were divided into five subgroups, including endocytic lysosomes and autophagic lysosomes and metabolic changes of various lysosomes in the aging process are studied.

In addition, the research group also analyzed the metabolic changes of the five lysosomal subsets in the aging process, and found that the metabonomics changes of each type of lysosomal subsets were different.

This work indicates that there exists lysosome type specificity in the changes of lysosome metabolism in the process of cell aging. Studying the heterogeneity of lysosome changes in the process of aging will attribute to solve the problems of cell aging and related diseases.

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