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EMBO J. 2014 Oct 1;33(19):2142-56. doi: 10.15252/embj.201488104. Epub 2014 Aug 8.

A new pathway for mitochondrial quality control: mitochondrial-derived vesicles.

Author information

1
Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
2
Montreal Neurological Institute, McGill University, Montreal, QC, Canada heidi.mcbride@mcgill.ca.

Abstract

The last decade has been marked by tremendous progress in our understanding of the cell biology of mitochondria, with the identification of molecules and mechanisms that regulate their fusion, fission, motility, and the architectural transitions within the inner membrane. More importantly, the manipulation of these machineries in tissues has provided links between mitochondrial dynamics and physiology. Indeed, just as the proteins required for fusion and fission were identified, they were quickly linked to both rare and common human diseases. This highlighted the critical importance of this emerging field to medicine, with new hopes of finding drugable targets for numerous pathologies, from neurodegenerative diseases to inflammation and cancer. In the midst of these exciting new discoveries, an unexpected new aspect of mitochondrial cell biology has been uncovered; the generation of small vesicular carriers that transport mitochondrial proteins and lipids to other intracellular organelles. These mitochondrial-derived vesicles (MDVs) were first found to transport a mitochondrial outer membrane protein MAPL to a subpopulation of peroxisomes. However, other MDVs did not target peroxisomes and instead fused with the late endosome, or multivesicular body. The Parkinson's disease-associated proteins Vps35, Parkin, and PINK1 are involved in the biogenesis of a subset of these MDVs, linking this novel trafficking pathway to human disease. In this review, we outline what has been learned about the mechanisms and functional importance of MDV transport and speculate on the greater impact of these pathways in cellular physiology.

KEYWORDS:

PINK1; Parkin; mitochondria; quality control; vesicle transport

PMID:
25107473
PMCID:
PMC4282503
DOI:
10.15252/embj.201488104
[Indexed for MEDLINE]
Free PMC Article

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