Immunoregulatory Effects of Mitochondria Transferred by Extracellular Vesicles

Abstract

Mitochondria participate in immune regulation through various mechanisms, such as changes in the mitochondrial dynamics, as metabolic mediators of the tricarboxylic acid cycle, by the production of reactive oxygen species, and mitochondrial DNA damage, among others. In recent years, studies have shown that extracellular vesicles are widely involved in intercellular communication and exert important effects on immune regulation. Recently, the immunoregulatory effects of mitochondria from extracellular vesicles have gained increasing attention. In this article, we review the mechanisms by which mitochondria participate in immune regulation and exert immunoregulatory effects upon delivery by extracellular vesicles. We also focus on the influence of the immunoregulatory effects of mitochondria from extracellular vesicles to further shed light on the underlying mechanisms.

Keywords: extracellular vesicles; immune cell; immunoregulation; mesenchymal stem cells; mitochondria.

Figure 1

Immunomodulatory effects of mitochondria. Mitochondria undergo (A) dynamic changes: The electron transport chains of split and fused mitochondria are different and tend to produce ROS and ATP, respectively; (B) metabolic medium of the tricarboxylic acid cycle: blockade of the tricarboxylic acid cycle leads to accumulation of inflammatory substances; (C) ROS production: mitochondrial ROS are important bactericidal substances of macrophages; (D) DNA damage participates in immune regulation: mtDNAs participate in immune responses by serving as DAMPs. ETC, electron transport chain; BA, bactericidal; ROS, reactive oxygen species; FAO, fatty acid oxidation; OXPHOS, oxidative phosphorylation; NLRP3, NACHT, LRR, and PYD domain-containing protein 3; DAMPs, damage-associated molecular patterns; cGAS, cyclic GMP-AMP synthase; STING, stimulator of interferon genes; TBK1, TANK-binding kinase 1.

Figure 2

Mitochondria regulate immune cell via extracellular vesicles. Mediated by ARRDC1, mitochondria communicate between cells with the help of extracellular vesicles to modulate cellular functions. ARRDC1, arrestin domain-containing protein 1.