MitoEVs: A new player in multiple disease pathology and treatment

Abstract

Mitochondrial damage plays vital roles in the pathology of many diseases, such as cancers, neurodegenerative diseases, aging, metabolic diseases and many types of organ injury. However, the regulatory mechanism of mitochondrial functions among different cells or organs in vivo is still unclear, and efficient therapies for attenuating mitochondrial damage are urgently needed. Extracellular vesicles (EVs) are cell‐derived nanovesicles that can deliver bioactive cargoes among cells or organs. Interestingly, recent evidence shows that diverse mitochondrial contents are enriched in certain EV subpopulations, and such mitoEVs can deliver mitochondrial components to affect the functions of recipient cells under different conditions, which has emerged as a hot topic in this field. However, the overview and many essential questions with respect to this event remain elusive. In this review, we provide a global view of mitoEVs biology and mainly focus on the detailed sorting mechanisms, functional mitochondrial contents, and diverse biological effects of mitoEVs. We also discuss the pathogenic or therapeutic roles of mitoEVs in different diseases and highlight their potential as disease biomarkers or therapies in clinical translation. This review will provide insights into the pathology and drug development for various mitochondrial injury‐related diseases.

A complex interplay of intra- and extracellular factors regulates the outcome of fetal- and adult-derived MLL-rearranged leukemia

“…S5F ). For example, four members of NADH dehydrogenase (Ndufa2, Ndufa7, Ndufs5, and Ndufv3) were all uniquely present in the BMEF (Table S3 ), indicating specific extracellular function for these metabolic enzymes in BMEF and possible unique regulation of the leukemia microenvironment of adults, as suggested for other cancers [ 52 ].…”

Nutrient availability regulates the secretion and function of immune cell–derived extracellular vesicles through metabolic rewiring

“…For instance, mitochondrial respiratory defects and mtROS overproduction under hyperglycemic conditions induce NF-κB/p38 MAPK pathway and cytokine (e.g., TNF-α and IL-6) production in Mφs ( 41 ). Likewise, mitochondrial stress caused by mitochondrial Lon overexpression promoted the secretion of EVs harboring mtDNA in cancer cells ( 44 ). Consistently, M1-Mφs in the GLN − group exhibited impaired mitochondrial oxidative metabolism, as indicated by increased mtROS and decreased mitochondrial membrane potential and ATP compared to those in the GLN + group ( Fig.…”

MELAS-Derived Neurons Functionally Improve by Mitochondrial Transfer from Highly Purified Mesenchymal Stem Cells (REC)

“…EVs are essential intercellular communication vectors for the transfer of bioactive substances between cells and organs. Recently, abundant evidence has shown that mitochondria-derived vesicles (MDVs, ~70-150 nm) or intact mitochondrial translocation is mainly mediated by multivesicular bodies (MVBs, ~30-150 nm) and MVs (~200-1000 nm) and that vesicle formation as well as release cannot be separated from the role of endocytosis in cells [28]. We used dynasore to inhibit the formation and release of MVBs and MVs, thereby inhibiting mitochondrial transfer and reception.…”

“…Recent studies have shown that some subtypes of extracellular vesicles (EVs) can carry mitochondrial components from cell to cell (i.e., mitoEVs) and that complete parallel transfer of mitochondria can occur via MVs [28]. Dynasore, an inhibitor of the endocytic pathway, rapidly blocks the formation of coated vesicles, thereby preventing the delivery and reception of mitochondria as MVs.…”