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

Abstract

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.

Mitochondrial transplantation and its impact on infectious disease progression: a pilot study

“…These experiments, taken together, correspond accurately to our predictions and to the in-vitro work done in parallel at our partner lab at the University of Laval Quebec. 68,32 We expected to see that mitochondria transplanted from younger to older mice would create a much more profound beneficial effect. We expected that mitlets would provide a robust response while liver-isolated mitochondria would produce little or no response because mitlets are preferentially targeted to immune cells, while liver mitochondria, with no vesicle and no receptors, become scattered into different tissues.…”

“…We interpret this to mean that the recipient white blood cells, although they received mitochondria of approximately the same functionality as those they already had, nevertheless benefited by getting additional mitochondria. According to our in-vivo studies 68 , white blood cells have a certain “starting complement” of existing mitochondria. In the middle of an infection, the white blood cells might have the capacity to accept additional mitochondria – again, corresponding to our earlier analogy of mitochondria as a type of spare battery pack.…”

Mitochondrial transfer and implications for muscle function in idiopathic inflammatory myopathies

“…Mitochondria, central to cellular energy dynamics, calcium homeostasis, and apoptosis, play a fundamental role in muscle tissues, where they cater to high-energy demands and foster muscle health (38,39). Recent years have witnessed significant advances in our understanding of mitochondrial functions, chiefly the phenomenon of mitochondrial transfer, a process through which mitochondria are relocated between cells, indicating a new dimension in intercellular communication and cooperation for modulating inflammatory response (40)(41)(42). With its implications in muscle physiology, this transfer process hints at potential transformative approaches to muscle regeneration and repair, thereby inciting substantial research efforts aimed at delineating the pathways that facilitate these transfers and understanding their therapeutic ramifications (43,44).…”

“…Mitochondrial transfer is a technique that refers to the delivery of either intact mitochondria, or mitochondrial components, such as RNA, DNA, or proteins, from one cell to another (40,87). Preliminary studies have highlighted the significant potential of mitochondrial transfer for the regeneration of damaged tissues and alleviation of symptoms in various diseases and tissues, including the heart, skeletal muscle, and even immune cells (41,44,88). Mitochondrial transfer reduces ROS emissions and improves cellular respiration, suggesting that mitochondrial trafficking and bioenergetic reprogramming could be effective in maintaining tissue homeostasis and treating various diseases (89).…”