Cell Death and Disease (Apr 2023)

Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways

  • Zhen Xie,
  • Mengyuan Zhao,
  • Chengxiang Yan,
  • Wei Kong,
  • Fei Lan,
  • Narengaowa,
  • Shuxuan Zhao,
  • Qinghu Yang,
  • Zhantao Bai,
  • Hong Qing,
  • Junjun Ni

DOI
https://doi.org/10.1038/s41419-023-05786-0
Journal volume & issue
Vol. 14, no. 4
pp. 1 – 18

Abstract

Read online

Abstract Cathepsin B (CatB), a cysteine protease, is primarily localized within subcellular endosomal and lysosomal compartments. It is involved in the turnover of intracellular and extracellular proteins. Interest is growing in CatB due to its diverse roles in physiological and pathological processes. In functional defective tissues, programmed cell death (PCD) is one of the regulable fundamental mechanisms mediated by CatB, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death. However, CatB-mediated PCD is responsible for disease progression under pathological conditions. In this review, we provide an overview of the critical roles and regulatory pathways of CatB in different types of PCD, and discuss the possibility of CatB as an attractive target in multiple diseases. We also summarize current gaps in the understanding of the involvement of CatB in PCD to highlight future avenues for research.