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TitleProteomic Profiling of Mitochondrial-Derived Vesicles in Brain Reveals Enrichment of Respiratory Complex Sub-assemblies and Small TIM Chaperones.
Publication TypeJournal Article
Year of Publication2021
AuthorsRoberts, Rosalind F., Andrew N. Bayne, Thomas Goiran, Dominique Lévesque, François-Michel Boisvert, Jean-François Trempe, and Edward A. Fon
JournalJ Proteome Res
Volume20
Issue1
Pagination506-517
Date Published2021 Jan 01
ISSN1535-3907
Abstract

The generation of mitochondrial-derived vesicles (MDVs) is implicated in a plethora of vital cell functions, from mitochondrial quality control to peroxisomal biogenesis. The discovery of distinct subtypes of MDVs has revealed the selective inclusion of mitochondrial cargo in response to varying stimuli. However, the true scope and variety of MDVs is currently unclear, and unbiased approaches have yet to be used to understand their biology. Furthermore, as mitochondrial dysfunction has been implicated in many neurodegenerative diseases, it is essential to understand MDV pathways in the nervous system. To address this, we sought to identify the cargo in brain MDVs. We used an budding assay and proteomic approach to identify proteins selectively enriched in MDVs. 72 proteins were identified as MDV-enriched, of which 31% were OXPHOS proteins. Interestingly, the OXPHOS proteins localized to specific modules of the respiratory complexes, hinting at the inclusion of sub-assemblies in MDVs. Small TIM chaperones were also highly enriched in MDVs, linking mitochondrial chaperone-mediated protein transport to MDV formation. As the two Parkinson's disease genes PINK1 and Parkin have been previously implicated in MDV biogenesis in response to oxidative stress, we compared the MDV proteomes from the brains of wild-type mice with those of PINK1 and Parkin mice. No significant difference was found, suggesting that PINK1- and Parkin-dependent MDVs make up a small proportion of all MDVs in the brain. Our findings demonstrate a previously uncovered landscape of MDV complexity and provide a foundation from which further novel MDV functions can be discovered. Data are available via ProteomeXchange with identifier PXD020197.

DOI10.1021/acs.jproteome.0c00506
Alternate JournalJ Proteome Res
PubMed ID33242952