2. Academic Validation
  3. Metabolomic profiling of single enlarged lysosomes

Metabolomic profiling of single enlarged lysosomes

  • Nat Methods. 2021 Jul;18(7):788-798. doi: 10.1038/s41592-021-01182-8.
Hongying Zhu  # 1,  Qianqian Li  # 1,  Tiepeng Liao  # 1,  Xiang Yin 1,  Qi Chen 1,  Ziyi Wang 1,  Meifang Dai 1,  Lin Yi 1,  Siyuan Ge 1,  Chenjian Miao 1,  Wenping Zeng 1,  Lili Qu 1,  Zhenyu Ju 2,  Guangming Huang 3,  Chunlei Cang 4 5,  Wei Xiong 6 7 8
Affiliations

Affiliations

  • 1 Institute on Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China.
  • 2 Key Laboratory of Regenerative Medicine of Ministry of Education, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Institute of Aging and Regenerative Medicine, Jinan University, Guangdong, China.
  • 3 Department of Chemistry, School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, China.
  • 4 Institute on Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China. ccang@ustc.edu.cn.
  • 5 The CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, Hefei, China. ccang@ustc.edu.cn.
  • 6 Institute on Aging and Brain Disorders, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, China. wxiong@ustc.edu.cn.
  • 7 Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China. wxiong@ustc.edu.cn.
  • 8 Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. wxiong@ustc.edu.cn.
  • # Contributed equally.
PMID: 34127857 DOI: 10.1038/s41592-021-01182-8
Abstract

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic Amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes.

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