The interplay between copper metabolism and microbes: in perspective of host copper-dependent ATPases ATP7A/B

Front Cell Infect Microbiol. 2023 Nov 30:13:1267931. doi: 10.3389/fcimb.2023.1267931. eCollection 2023.

Abstract

Copper, a vital element in various physiological processes, is transported from the gastrointestinal tract to tissues and cells through diverse copper transporters. Among these transporters, ATP7A and ATP7B play significant roles in regulating systemic copper metabolism and exhibit precise regulation in their intracellular trafficking. These transporters undergo dynamic shuttling between the trans-Golgi network (TGN) and the plasma membrane via the endocytic recycling mechanism, which involves the retromer and other associated factors. Interestingly, the antimicrobial attribute of copper implies a potential connection between microbial infection and copper metabolism. Several microbes, including Salmonella enterica, Cryptococcus, Influenza A virus (IAV) and Zika virus (ZIKV) have been observed to impact the regulatory mechanisms of ATP7A/B, either directly or indirectly, as a means of survival. This review summarizes the key features and trafficking mechanisms of the copper transporters ATP7A/B, and examines the intricate interplay between microbes and copper metabolism. Ultimately, it highlights how microbes can perturb copper homeostasis through interactions with host factors, offering valuable insights into the mechanistic aspects of host-microbe interactions.

Keywords: ATP7A; ATP7B; copper metabolism; membrane trafficking; microbes.

Publication types

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

MeSH terms

  • Adenosine Triphosphatases
  • Cation Transport Proteins* / metabolism
  • Copper / metabolism
  • Copper Transport Proteins
  • Copper-Transporting ATPases / metabolism
  • Humans
  • Peptide Fragments / metabolism
  • Zika Virus Infection*
  • Zika Virus*

Substances

  • Copper
  • Adenosine Triphosphatases
  • Cation Transport Proteins
  • Copper Transport Proteins
  • ATP7A protein, human
  • Copper-Transporting ATPases
  • ATP7A protein, human (2-79)
  • Peptide Fragments

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from National Natural Science Foundation of China (82272306 and 82072270), College Students’ Innovative Entrepreneurial Training Plan Program (202210439002), Taishan Scholars Program (tstp20221142), and Academic Promotion Program of Shandong First Medical University (2019LJ001).