Selective Packaging of Mitochondrial Proteins into Extracellular Vesicles Prevents the Release of Mitochondrial DAMPs

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Vesicles containing selective mitochondrial cargo are found in proximity to the plasma membrane (≤1 µm) but away from the main mitochondrial network (>1 µm)

News Release, World Mitochondria Society, Berlin - Germany – September 2, 2022

Most cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles. While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. 

  • Germain et al. demonstrated that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs.
  • They found that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways.
  • They showed that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes.

These results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.

Paper DOI.

© Image -Todkar et al., Nature Communications 2022

Dr. Marc Germain will join Targeting Mitochondria 2022 to extensively discuss those result in a session entitled "Extracellular Vesicles & Mitochondria: The Target". Conference Program.


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