Document Type
Journal Article
Publication Date
12-1-2017
Journal
Scientific Reports
Volume
7
Issue
1
DOI
10.1038/s41598-017-00039-5
Abstract
Most nuclear-encoded mitochondrial proteins traffic from the cytosol to mitochondria. Some of these proteins localize at mitochondria-associated membranes (MAM), where mitochondria are closely apposed with the endoplasmic reticulum (ER). We have previously shown that the human cytomegalovirus signal-anchored protein known as viral mitochondria-localized inhibitor of apoptosis (vMIA) traffics from the ER to mitochondria and clusters at the outer mitochondrial membrane (OMM). Here, we have examined the host pathways by which vMIA traffics from the ER to mitochondria and clusters at the OMM. By disruption of phosphofurin acidic cluster sorting protein 2 (PACS-2), mitofusins (Mfn1/2), and dynamin related protein 1 (Drp1), we find these conventional pathways for ER to the mitochondria trafficking are dispensable for vMIA trafficking to OMM. Instead, mutations in vMIA that change its hydrophobicity alter its trafficking to mitochondria. Superresolution imaging showed that PACS-2- and Mfn-mediated membrane apposition or hydrophobic interactions alter vMIA's ability to organize in nanoscale clusters at the OMM. This shows that signal-anchored MAM proteins can make use of hydrophobic interactions independently of conventional ER-mitochondria pathways to traffic from the ER to mitochondria. Further, vMIA hydrophobic interactions and ER-mitochondria contacts facilitate proper organization of vMIA on the OMM.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Salka, K., Bhuvanendran, S., Wilson, K., Bozidis, P., Mehta, M., Rainey, K., Sesaki, H., Patterson, G., Jaiswal, J. K., & Colberg-Poley, A. M. (2017). Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport.. Scientific Reports, 7 (1). http://dx.doi.org/10.1038/s41598-017-00039-5
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of Macmillan Publishers Ltd. Scientific Reports