The critical roles of STING in mitochondrial homeostasis

Biochem Pharmacol. 2024 Feb:220:115938. doi: 10.1016/j.bcp.2023.115938. Epub 2023 Dec 10.

Abstract

The stimulator of interferon genes (STING) is a crucial signaling hub in the immune system's antiviral and antimicrobial defense by detecting exogenous and endogenous DNA. The multifaceted functions of STING have been uncovered gradually during past decades, including homeostasis maintenance and overfull immunity or inflammation induction. However, the subcellular regulation of STING and mitochondria is poorly understood. The main functions of STING are outlined in this review. Moreover, we discuss how mitochondria and STING interact through multiple mechanisms, including the release of mitochondrial DNA (mtDNA), modulation of mitochondria-associated membrane (MAM) and mitochondrial dynamics, alterations in mitochondrial metabolism, regulation of reactive oxygen species (ROS) production, and mitochondria-related cell death. Finally, we discuss how STING is crucial to disease development, providing a novel perspective on its role in cellular physiology and pathology.

Keywords: Cell death; Innate immunity; Mitochondrial dynamics; Mitochondrial metabolism; MtDNA; STING.

Publication types

  • Review

MeSH terms

  • DNA, Mitochondrial* / genetics
  • DNA, Mitochondrial* / metabolism
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Inflammation / metabolism
  • Mitochondria* / metabolism
  • Signal Transduction

Substances

  • DNA, Mitochondrial
  • STING1 protein, human