Mitochondria 101: Mitochondrial Interaction Network

Identification: Shoubridge, Eric


Mitochondria 101: Mitochondrial Interaction Network      
Hana Antonicka1, Zhen-Yuan Lin2, Anne-Claude Gingras2, Eric A. Shoubridge1
1Montreal Neurological Institute & McGill University; Montreal, Quebec, Canada; 2Lunenfeld-Tanenbaum Research Institute & University of Toronto; Toronto, Ontario, Canada
Mitochondria play many important cellular functions besides the production of energy. They are indispensable for heme biogenesis, calcium and lipid homeostasis, and are part of signaling pathways in cell death and innate immunity. Mitochondria are also very dynamic organelles that maintain contact with endoplasmic reticulum and other cellular compartments, and are involved in cellular trafficking and peroxisomal biogenesis. Understanding how mitochondria integrate these distinct functional demands in different cell types is crucial to understanding the extraordinary clinical heterogeneity associated with mitochondrial diseases.
To better comprehend the role of individual functional networks within mitochondria and between mitochondria and the remainder of the cell, we decided to establish a mitochondrial interaction network using a proximity biotinylation assay, BioID. BioID uses a promiscuous biotin ligase covalently fused to a protein of interest (bait), which subsequently biotinylates proteins in the vicinity of the bait. To date, we have analyzed 101 mitochondrial baits that interacted with ~620 known mitochondrial proteins and ~1410 other proteins (BFDR<0.02). These data enabled us to create functional networks within individual mitochondrial compartments, establish the relationships between these networks as well as discover novel roles for proteins both within and outside the mitochondria. Our data clearly show that by using BioID we can identify novel, previously uncharacterized mitochondrial proteins and determine their localization within the mitochondrion as well as within a functional network. Interrogation of interactions of outer mitochondrial membrane proteins enabled us to define their involvement in the formation of contact sites with other cellular organelles. In addition, we investigated how individual interactomes change when mutant protein variants are present, yielding insight into possible pathogenic mechanisms and potential treatment targets.
Acknowledgements; Funding by grants from the Canadian Institutes for Health Research and the United Mitochondrial Disease Foundation.


Credits: None available.

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