The oxysterol‐binding protein (OSBP)‐related proteins ORP5 and ORP8 have been shown recently to transport phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM) at ER–PM contact sites. PS is also transferred from the ER to mitochondria where it acts as precursor for mitochondrial PE synthesis. Here, we show that, in addition to ER–PM contact sites, ORP5 and ORP8 are also localized to ER–mitochondria contacts and interact with the outer mitochondrial membrane protein PTPIP51. A functional lipid transfer (ORD) domain was required for this localization. Interestingly, ORP5 and ORP8 depletion leads to defects in mitochondria morphology and respiratory function.
This study provides evidence for a novel localization of the PS lipid transfer proteins ORP5 and ORP8 at ER–mitochondria contact sites, in addition to ER–PM contacts. Depletion of ORP5 and ORP8 leads to defects in mitochondria morphology and respiratory function.
In addition to ER–PM contact sites, ORP5 and ORP8 also localize at ER–mitochondria contacts.
ORP5/ORP8 interacts with the mitochondrial protein PTPIP51.
ORP5/ORP8 targeting to ER–mitochondria contact sites and interaction with mitochondrial protein PTPIP51 depends on their lipid binding/transfer ability.
ORP5/ORP8 is involved in the maintenance of mitochondria morphology and respiratory function.
EMBO Reports (2016) 17: 800–810
- Received July 30, 2015.
- Revision received March 4, 2016.
- Accepted March 9, 2016.
- © 2016 The Authors