Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport

Kyle Salka, Shivaprasad Bhuvanendran, Kassandra Wilson, Petros Bozidis, Mansi Mehta, Kristin Rainey, Hiromi Sesaki, George Patterson, Jyoti Jaiswal, Anamaris Colberg-Poley

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number16
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Feb 2 2017

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Mitochondrial Proteins
Mitochondrial Membranes
Protein Transport
Endoplasmic Reticulum
Mitochondria
Membrane Proteins
Apoptosis
Hydrophobic and Hydrophilic Interactions
Dynamin II
Proteins
Membranes
Cytomegalovirus

ASJC Scopus subject areas

  • General

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Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport. / Salka, Kyle; Bhuvanendran, Shivaprasad; Wilson, Kassandra; Bozidis, Petros; Mehta, Mansi; Rainey, Kristin; Sesaki, Hiromi; Patterson, George; Jaiswal, Jyoti; Colberg-Poley, Anamaris.

In: Scientific Reports, Vol. 7, No. 1, 16, 02.02.2017.

Research output: Contribution to journalArticle

Salka, Kyle ; Bhuvanendran, Shivaprasad ; Wilson, Kassandra ; Bozidis, Petros ; Mehta, Mansi ; Rainey, Kristin ; Sesaki, Hiromi ; Patterson, George ; Jaiswal, Jyoti ; Colberg-Poley, Anamaris. / Superresolution Imaging Identifies That Conventional Trafficking Pathways Are Not Essential for Endoplasmic Reticulum to Outer Mitochondrial Membrane Protein Transport. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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