Mitochondrial-derived vesicles

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Heidi McBride's group with Edward Fon (Soubannier et al., Curr Biol 2012; McLelland et al., EMBO J 2014); Diana Matheoud, Michel Desjardins, McBride, Louis-Éric Trudeau and colleagues (Matheoud et al., Cell 2016; Nature 2019). Funders were not checked.

What happened

• Vesicle pathway. Mitochondria can bud off small vesicles (mitochondrial-derived vesicles, MDVs) that carry damaged proteins to lysosomes for disposal. Soubannier et al. (2012) showed MDVs deliver cargo to lysosomes, rise early under oxidative stress and do not need the autophagy proteins ATG5 or LC3. McLelland et al. (2014) showed this runs separately from full mitophagy. It is triggered by oxidative stress inside mitochondria and needs working PINK1 and parkin. A Parkinson's-linked parkin mutant did not support it.
• Immune link (2016). Matheoud et al. found that PINK1 and parkin actively suppress MDV formation and a process they named mitochondrial antigen presentation, where immune cells display mitochondrial fragments on their surface. Without PINK1 or parkin, inflammatory conditions triggered it in cells and in mice. It needs Rab9 and sorting nexin 9. The authors present this as a possible autoimmune route, which commentaries call a hypothesis.
• Follow-up (2019). Matheoud et al. (Nature) found that gut infection with Gram-negative bacteria in Pink1-knockout mice triggered mitochondria-specific cytotoxic T cells in the body and brain, loss of dopamine nerve endings in the striatum, and movement problems that L-DOPA reversed. It is still mouse work.

Keep this separate from landmark 54: that STING paper (Sliter et al., from Richard Youle's group) was retracted in 2025. The retraction note concerns that paper's own figures; the MDV papers are different work from different groups, and no correction or retraction was found for them in Europe PMC.

Why it moved us toward a cure

It extends the mitophagy story of landmark 15 and the parkin gene of landmark 12 with a second quality-control route, and links it to immunity. This points to immune-based approaches in people with parkin or PINK1 mutations.

Outcome

Open. All evidence is from cells and mice (including the 2019 infection model). No human proof, no drug.

Sources

• Soubannier et al., Curr Biol 2012;22:135–141, DOI 10.1016/j.cub.2011.11.057, PubMed 22226745
• McLelland et al., EMBO J 2014;33:282–295, DOI 10.1002/embj.201385902, PubMed 24446486 (PMC3989637)
• Matheoud et al., Cell 2016;166:314–327, DOI 10.1016/j.cell.2016.05.039, PubMed 27345367 · Roberts and Fon commentary (PMC5099861)
• Matheoud et al., Nature 2019;571:565–569, DOI 10.1038/s41586-019-1405-y, PubMed 31316206
• Retraction Note, Sliter et al., Nature 2025, DOI 10.1038/s41586-025-09346-8 (for the separate STING paper)
• Not yet verified: full texts (abstracts only); the Sugiura review (EMBO J 2014); independent replication of mitochondrial antigen presentation by a group outside the Montreal network.