The diversity and coexistence of extracellular mitochondria in circulation: A friend or foe of the immune system

Caicedo, Andrés; Zambrano, Kevin; Sanon, Serena; Vélez, Jorge Luis; Montalvo, Mario; Jara, Fernando; Moscoso, Santiago Aguayo; Páez, Pablo Andrés Vélez; Maldonado, Augusto; Velarde, Gustavo

doi:10.1016/j.mito.2021.02.014

Cited by 31 publications

(9 citation statements)

References 103 publications

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“…Extracellular mitochondria are described as increased in certain inflammatory conditions, consistent with cellular activation 13,56,57 . Their release may promote the repair of damaged tissues following an inflammatory condition 32 .…”

Section: Discussionmentioning

confidence: 88%

“…Extracellular mitochondria are described as increased in certain inflammatory conditions, consistent with cellular activation. 13,56,57 Their release may promote the repair of damaged tissues following an inflammatory condition. 32 In systemic lupus erythematosus, platelets release their mitochondria 13 ; however, these patients display higher levels of antibodies directed against epitopes of the mitochondrial outer membrane, such as the mitochondrial mitofusin-1.…”

Section: Discussionmentioning

confidence: 99%

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Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

Pelletier,

Breton,

Allaeys

et al. 2023

Transfusion

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BackgroundMitochondria play a critical role in the production of cell energy and the regulation of cell death. Therefore, mitochondria orchestrate numerous cell effector functions, including fine‐tuning the immune system. While mitochondria are mainly found intracellularly, they can escape the confine of the cell during the process of extracellular vesicle release. Platelets patrol blood vessels to ensure vasculature integrity and to support the immune system. In blood, platelets are the primary source of circulating mitochondria. Activated platelets produce extracellular vesicles, including a subset of mitochondria‐containing vesicles.Study Design and MethodsWe characterized mitochondrial functions in platelet‐derived extracellular vesicles, and examined whether they could impact the bioenergetics of cellular immune recipients using an extracellular flux analyzer to measure real‐time bioenergetics.ResultsWe validated that extracellular vesicles derived from activated platelets contain the necessary mitochondrial machinery to respirate and generate energy. Moreover, neutrophils and monocytes efficiently captured platelet‐derived extracellular vesicles, enhancing their mitochondrial fitness. This process required functional mitochondria from donor platelets, as it was abolished by the inactivation of extracellular mitochondria using mitochondrial poison.DiscussionTogether, the data suggest that extracellular mitochondria produced by platelets may support other metabolic functions through transcellular bioenergetics.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

Pelletier,

Breton,

Allaeys

et al. 2023

Transfusion

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“…In addition, because DAMPs and dysfunctional mtDNA exacerbate inflammation by triggering innate immune responses, which contribute to the onset and pathological processing of NDDs, therapeutic strategies have been aimed at reducing cytosolic mtDNA accumulation and inhibiting molecules of the downstream signaling pathway of DAMP [ 212 , 213 ]. On the other hand, healthy mtDNA is able to activate the mesenchymal stem cell pathway, which transfers healthy extracellular mitochondria via vesicles to damaged cells, thereby revitalizing the metabolic activity of nearby cells [ 214 - 217 ]. In our recent study, transplanted mitochondria led to the reuptake of extracellular mtDNA, resulting in improved mtDNA homeostasis [ 218 ].…”

Section: Conclusion and Future Perspectivementioning

confidence: 99%

mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases

Shang

Huang

Wang

et al. 2023

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Considerable evidence indicates that the semiautonomous organelles mitochondria play key roles in the progression of many neurodegenerative disorders. Mitochondrial DNA (mtDNA) encodes components of the OXPHOS complex but mutated mtDNA accumulates in cells with aging, which mirrors the increased prevalence of neurodegenerative diseases. This accumulation stems not only from the misreplication of mtDNA and the highly oxidative environment but also from defective mitophagy after fission. In this review, we focus on several pivotal mitochondrial proteins related to mtDNA maintenance (such as ATAD3A and TFAM), mtDNA alterations including mtDNA mutations, mtDNA elimination, and mtDNA release-activated inflammation to understand the crucial role played by mtDNA in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. Our work outlines novel therapeutic strategies for targeting mtDNA.

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“…Mitochondrial components can be extruded from cells within two types of EVs (Caicedo et al, 2021). One type of small vesicles (~30-250 nm) called exosomes are formed in the endosomal compartment and are surrounded by the common membrane forming MVBs.…”

Section: Intercellular Signaling With Evs and Mitochondrial Transfermentioning

confidence: 99%

Extrusion of mitochondria: Garbage clearance or cell–cell communication signals?

Lyamzaev

Zinovkin

Chernyak

2022

Journal Cellular Physiology

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Mitochondria are dynamic organelles that regulate various intracellular signaling pathways, including the mechanisms of programmed cell death, differentiation, inflammation, and so on. Mitochondria may be extruded as membrane enveloped or as free organelles during developmental processes, inflammatory activation, and in the process of “garbage clearance” of damaged mitochondria in postmitotic cells. Extracellular mitochondria can be engulfed by immune and nonimmune cells and trigger intracellular signaling leading to an inflammatory response. At the same time, it was reported that the release of extracellular vesicles containing mitochondria from mesenchymal stem cells contributes to their therapeutic anti‐inflammatory effects. Numerous studies claim that engulfed mitochondria improve cellular bioenergetics, but this assumption requires further investigation. This review aims at a critical discussion of the mechanisms of mitochondrial extrusion in mammals, the reception of mitochondrial components, and the responses of recipient cells to extracellular mitochondria.

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The diversity and coexistence of extracellular mitochondria in circulation: A friend or foe of the immune system

Cited by 31 publications

References 103 publications

Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

Platelet extracellular vesicles and their mitochondrial content improve the mitochondrial bioenergetics of cellular immune recipients

mtDNA Maintenance and Alterations in the Pathogenesis of Neurodegenerative Diseases

Extrusion of mitochondria: Garbage clearance or cell–cell communication signals?

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