Should it stay or should it go: gap junction protein GJA1/Cx43 conveys damaged lysosomes to the cell periphery to potentiate exocytosis

Autophagy. 2024 Dec;20(12):2816-2818. doi: 10.1080/15548627.2024.2408711. Epub 2024 Oct 21.

Abstract

GJA1/Cx43 (gap junction protein alpha 1) has long been associated with gap junctions-mediated communication between adjacent cells. However, recent data have defied this concept, with studies implicating GJA1 in other biological processes, such as macroautophagy/autophagy regulation, mitochondrial activity and extracellular vesicles biology. In our recent study we unveiled an additional role played by GJA1 in lysosomal trafficking. We demonstrate that GJA1 promotes the exocytosis of damaged lysosomes, through a mechanism that relies on ACTR2/ARP2-ACTR3/ARP3-dependent actin remodeling. Our findings ascribe to GJA1 an important role during pathogen infection and lysosomal storage disorders, favoring the release of dysfunctional lysosomes.

Keywords: Actin; Arp2; gap junction protein alpha 1/Connexin43; lysophagy; lysosomal damage; lysosomal exocytosis.

MeSH terms

  • Animals
  • Autophagy / physiology
  • Connexin 43* / metabolism
  • Exocytosis* / physiology
  • Gap Junctions / metabolism
  • Humans
  • Lysosomes* / metabolism

Substances

  • Connexin 43
  • GJA1 protein, human

Grants and funding

This work was supported by the COMPETE-UIDB/04539/2020.