Protein lipoylation: mitochondria, cuproptosis, and beyond

Cheng-Han Lin; Yeh Chin; Ming Zhou; Robert W Sobol; Mien-Chie Hung; Ming Tan

doi:10.1016/j.tibs.2024.04.002

Protein lipoylation: mitochondria, cuproptosis, and beyond

Trends Biochem Sci. 2024 May 6:S0968-0004(24)00096-3. doi: 10.1016/j.tibs.2024.04.002. Online ahead of print.

Authors

Cheng-Han Lin¹, Yeh Chin¹, Ming Zhou², Robert W Sobol³, Mien-Chie Hung⁴, Ming Tan⁵

Affiliations

¹ Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, China Medical University, Taichung, Taiwan.
² Cancer Research Institute and School of Basic Medical Sciences, Central South University, Changsha, China.
³ Department of Pathology and Laboratory Medicine, Warren Alpert Medical School and Legorreta Cancer Center, Brown University, Providence, RI 02912, USA.
⁴ Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, China Medical University, Taichung, Taiwan. Electronic address: mhung@mail.cmu.edu.tw.
⁵ Institute of Biochemistry and Molecular Biology, China Medical University, Taichung, Taiwan; Cancer Biology and Precision Therapeutics Center, China Medical University, Taichung, Taiwan; Graduate Institute of Biomedical Sciences and Research Center for Cancer Biology, China Medical University, Taichung, Taiwan. Electronic address: mingtan@mail.cmu.edu.tw.

PMID: 38714376
DOI: 10.1016/j.tibs.2024.04.002

Abstract

Protein lipoylation, a crucial post-translational modification (PTM), plays a pivotal role in mitochondrial function and emerges as a key player in cell death through cuproptosis. This novel copper-driven cell death pathway is activated by excessive copper ions binding to lipoylated mitochondrial proteins, disrupting energy production and causing lethal protein aggregation and cell death. The intricate relationship among protein lipoylation, cellular energy metabolism, and cuproptosis offers a promising avenue for regulating essential cellular functions. This review focuses on the mechanisms of lipoylation and its significant impact on cell metabolism and cuproptosis, emphasizing the key genes involved and their implications for human diseases. It offers valuable insights into targeting dysregulated cellular metabolism for therapeutic purposes.

Keywords: cancer; cell death; iron-sulfur cluster; metabolism; metal ion; post-translational modification.

Publication types

Review