The Potential Use of Mitochondrial Extracellular Vesicles as Biomarkers or Therapeutical Tools

Abstract

The mitochondria play a crucial role in cellular metabolism, reactive oxygen species (ROS) production, and apoptosis. Aberrant mitochondria can cause severe damage to the cells, which have established a tight quality control for the mitochondria. This process avoids the accumulation of damaged mitochondria and can lead to the release of mitochondrial constituents to the extracellular milieu through mitochondrial extracellular vesicles (MitoEVs). These MitoEVs carry mtDNA, rRNA, tRNA, and protein complexes of the respiratory chain, and the largest MitoEVs can even transport whole mitochondria. Macrophages ultimately engulf these MitoEVs to undergo outsourced mitophagy. Recently, it has been reported that MitoEVs can also contain healthy mitochondria, whose function seems to be the rescue of stressed cells by restoring the loss of mitochondrial function. This mitochondrial transfer has opened the field of their use as potential disease biomarkers and therapeutic tools. This review describes this new EVs-mediated transfer of the mitochondria and the current application of MitoEVs in the clinical environment.

The Research Progress of Mitochondrial Transplantation in the Treatment of Mitochondrial Defective Diseases

“…Mitochondria are also transported from donor cells via EVs [23] and enter the cytoplasm of the recipient cells through endocytosis or fusion [24]. Zhang et al found that EV-mediated mitochondrial transfer from human umbilical cord-derived mesenchymal stem cells to okadaic acid-treated SH-SY5Y cells, an in vitro model of Alzheimer's disease, reversed apoptotic signaling, improved cellular immune response, and reduced oxidative stress [25].…”

Immunometabolism, extracellular vesicles and cardiac injury

“…EVs can also transport mitochondrial enzymes, mitochondrial DNA, parts of the electron transport chain, mitochondrial fragments, and whole mitochondria ( 61 ). The role of these “mitoEVs” carry many implications for inflammatory pathways, which are tightly regulated by mitochondrial function ( 62 ).…”

“…Delivery of whole mitochondria to macrophages via EVs also plays a critical role in macrophage polarization ( 63 ). Damaged mitochondria can be packaged into EVs and sent to neighboring cells for repair ( 61 ). For example, MSCs undergoing mitophagy package damaged mitochondria into EVs, which are delivered to neighboring macrophages that complete the process of mitophagy, resulting in enhanced OXPHOS and M2-like polarization ( 64 ).…”

“…For example, MSCs undergoing mitophagy package damaged mitochondria into EVs, which are delivered to neighboring macrophages that complete the process of mitophagy, resulting in enhanced OXPHOS and M2-like polarization ( 64 ). Furthermore, healthy mitochondria from apoptotic cells can be “recycled” after being taken up by macrophages, in which they promote an M2-like phenotype ( 61 ). Conversely, macrophages can “donate” their mitochondria to injured or dysfunctional tissue, such as neurons ( 65 ).…”

The Role of Extracellular Vesicles in Aging and Disease

“…The group of Borrás et al [ 8 ] highlights the potential use of mitochondrial extracellular vesicles as biomarkers or therapeutic tools, suggesting their relevance to various conditions. Mitochondria play a critical role in cellular functions such as metabolism, ROS production, and apoptosis.…”