Intracellular spatiotemporal metabolism in connection to target engagement

Jingwei Zhang; Zhixia Qiu; Yongjie Zhang; Guangji Wang; Haiping Hao

doi:10.1016/j.addr.2023.115024

Intracellular spatiotemporal metabolism in connection to target engagement

Adv Drug Deliv Rev. 2023 Sep:200:115024. doi: 10.1016/j.addr.2023.115024. Epub 2023 Jul 27.

Authors

Jingwei Zhang¹, Zhixia Qiu², Yongjie Zhang³, Guangji Wang⁴, Haiping Hao⁵

Affiliations

¹ State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
² Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
³ Clinical Pharmacokinetics Laboratory, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
⁴ State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China; Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, Research Unit of PK-PD Based Bioactive Components and Pharmacodynamic Target Discovery of Natural Medicine of Chinese Academy of Medical Sciences, China Pharmaceutical University, Nanjing, China. Electronic address: guangjiwang@hotmail.com.
⁵ State Key Laboratory of Natural Medicines, Key Laboratory of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, China. Electronic address: haipinghao@cpu.edu.cn.

PMID: 37516411
DOI: 10.1016/j.addr.2023.115024

Abstract

The metabolism in eukaryotic cells is a highly ordered system involving various cellular compartments, which fluctuates based on physiological rhythms. Organelles, as the smallest independent sub-cell unit, are important contributors to cell metabolism and drug metabolism, collectively designated intracellular metabolism. However, disruption of intracellular spatiotemporal metabolism can lead to disease development and progression, as well as drug treatment interference. In this review, we systematically discuss spatiotemporal metabolism in cells and cell subpopulations. In particular, we focused on metabolism compartmentalization and physiological rhythms, including the variation and regulation of metabolic enzymes, metabolic pathways, and metabolites. Additionally, the intricate relationship among intracellular spatiotemporal metabolism, metabolism-related diseases, and drug therapy/toxicity has been discussed. Finally, approaches and strategies for intracellular spatiotemporal metabolism analysis and potential target identification are introduced, along with examples of potential new drug design based on this.

Keywords: Diseases; Drug design; Spatiotemporal metabolism; Sub-cellular organelle; Target discovery.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Metabolic Networks and Pathways*
Organelles*