ORP5/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function.
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.
Institut Jacques Monod, CNRS, UMR7592, Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
Romain
R
Galmes
Institut Jacques Monod, CNRS, UMR7592, Sorbonne Paris Cité, Université Paris Diderot, Paris, France.
Audrey
A
Houcine
Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Alexander R
AR
van Vliet
Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Patrizia
P
Agostinis
Institut Jacques Monod, CNRS, UMR7592, Sorbonne Paris Cité, Université Paris Diderot, Paris, France francesca.giordano@ijm.fr cathy.jackson@ijm.fr.
Catherine L
CL
Jackson
Institut Jacques Monod, CNRS, UMR7592, Sorbonne Paris Cité, Université Paris Diderot, Paris, France francesca.giordano@ijm.fr cathy.jackson@ijm.fr.
Francesca
0000-0002-5942-1753
F
Giordano
D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D055785:Gene Knockdown Techniques; D006801:Humans; D050356:Lipid Metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism; D011987:Receptors, Steroid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098825:Oxysterol Binding Proteins
D024101:Mitochondrial Proteins; D011987:Receptors, Steroid; D000098825:Oxysterol Binding Proteins; D017027:Protein Tyrosine Phosphatases; C515449:RMDN3 protein, human
ORP; endoplasmic reticulum; lipid transfer proteins; membrane contact sites; mitochondria