The effect of extracellular vesicles on the regulation of mitochondria under hypoxia

Abstract

Mitochondria are indispensable organelles for maintaining cell energy metabolism, and also are necessary to retain cell biological function by transmitting information as signal organelles. Hypoxia, one of the important cellular stresses, can directly regulates mitochondrial metabolites and mitochondrial reactive oxygen species (mROS), which affects the nuclear gene expression through mitochondrial retrograde signal pathways, and also promotes the delivery of signal components into cytoplasm, causing cellular injury. In addition, mitochondria can also trigger adaptive mechanisms to maintain mitochondrial function in response to hypoxia. Extracellular vesicles (EVs), as a medium of information transmission between cells, can change the biological effects of receptor cells by the release of cargo, including nucleic acids, proteins, lipids, mitochondria, and their compositions. The secretion of EVs increases in cells under hypoxia, which indirectly changes the mitochondrial function through the uptake of contents by the receptor cells. In this review, we focus on the mitochondrial regulation indirectly through EVs under hypoxia, and the possible mechanisms that EVs cause the changes in mitochondrial function. Finally, we discuss the significance of this EV-mitochondria axis in hypoxic diseases.

Small Extracellular Vesicles from Head and Neck Squamous Cell Carcinoma Cells Carry a Proteomic Signature for Tumor Hypoxia

“…Moreover, several immunosuppressive proteins including PD-1, PD-L1, and CTLA-4 were found to be enriched in hypoxic sEVs, contributing to hypoxia-dependent modulation of anti-tumor immune responses [23,24]. These and other studies suggest that hypoxia induces major changes in the release of sEVs by the tumor and in their contents [21,25,26].…”

Mitochondria-containing Extracellular Vesicles (EV) Reduce Mouse Brain Infarct Sizes and EV/HSP27 Protect Ischemic Brain Endothelial Cultures

“…Mitochondria, the central metabolic hub of cells, are essential organelles especially in high metabolic rate organs such as the brain (68). Mitochondria regulate and are involved in critical cellular events such as the production of cellular energy by ATP synthesis, induction of apoptosis, cell reproduction, growth, and differentiation, calcium homeostasis, immune activation, and mitophagy (39,68,69). Therefore, it is essential to maintain the quantity and quality of mitochondria for cell survival and tissue homeostasis.…”

Extracellular Vesicles in Acute Kidney Injury and Clinical Applications

“…EVs can deliver donor cell information to either proximate or remote cells. Not only individual macromolecules but also a subcellular organelle in its entirety such as a mitochondrium can be transferred via an EV to a target cell [59,60]. Several mechanisms, such as endocytosis and membrane fusion are known to unload EV contents in the target cell interior.…”