Mitochondrial‐derived vesicles retain membrane potential and contain a functional ATP synthase

Abstract

Vesicular transport is a means of communication. While cells can communicate with each other via secretion of extracellular vesicles, less is known regarding organelle‐to organelle communication, particularly in the case of mitochondria. Mitochondria are responsible for the production of energy and for essential metabolic pathways in the cell, as well as fundamental processes such as apoptosis and aging. Here, we show that functional mitochondria isolated from Saccharomyces cerevisiae release vesicles, independent of the fission machinery. We isolate these mitochondrial‐derived vesicles (MDVs) and find that they are relatively uniform in size, of about 100 nm, and carry selective protein cargo enriched for ATP synthase subunits. Remarkably, we further find that these MDVs harbor a functional ATP synthase complex. We demonstrate that these vesicles have a membrane potential, produce ATP, and seem to fuse with naive mitochondria. Our findings reveal a possible delivery mechanism of ATP‐producing vesicles, which can potentially regenerate ATP‐deficient mitochondria and may participate in organelle‐to‐organelle communication.

mtDNA extramitochondrial replication mediates mitochondrial defect effects

“…Vesicle-related cytosolic mtDNAs including those mediated by MDVs tend to bind endosomal TLR9, triggering MyD88-dependent signaling to interferons and proinflammatory cytokines. 48 , 49 , 50 , 51 The mammalian cGAS-Sting and TLR9 signaling pathways correspond to Drosophila IMD and Toll pathways, respectively. However, in our dMerf4 RNAi case, cytosolic mtDNA only activated IMD but not the Toll pathway, implying that cytosolic mtDNA activates the fly innate immune response less possibly through MDVs.…”

Tollip deficiency exaggerates airway type 2 inflammation in mice exposed to allergen and influenza A virus: role of the ATP/IL-33 signaling axis

“…A previous study ( 28 ) suggests that Tollip by interacting with an E3 ubiquitin ligase Parkin is critical to coordinate the delivery of mitochondrial-derived vesicles (MDVs) to lysosomes for degradation. Therefore, it is possible that Tollip deficiency may result in impaired clearance of MDVs containing ATP synthase ( 69 ), leading to increased production of extracellular ATP. The accumulated extracellular ATP subsequently increases the release of IL-33 to enhance type 2 inflammation.…”

Mitochondria-derived Vesicles mediate Mito-nuclear Trafficking of Cargo

“…But, in the case of the widely studied TOM20 + MDVs, MIRO1/2 and Drp1 are required for MDV formation [14]. MDVs thus generated play a variety of roles including peroxisome biogenesis, mitochondrial quality control, mitochondrial antigen presentation, bacterial killing within phagosomes and in the regeneration of ATP deficient mitochondria [3,6,10,15,16]. However, MDVs have not been implicated in mito-nuclear cargo transit which we explore here.…”