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ORP5 Transfers Phosphatidylserine to Mitochondria and Regulates Mitochondrial Calcium Uptake at Endoplasmic Reticulum - Mitochondria Contact Sites

69 Pages Posted: 9 Sep 2019 Sneak Peek Status: Review Complete

See all articles by Leila Rochin

Leila Rochin

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

Cécile Sauvanet

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

Eeva Jääskeläinen

Minerva Foundation Institute for Medical Research

Audrey Houcine

Université Paris VII Denis Diderot - IJM - Institut Jacques Monod

Annukka Kivela

Minerva Foundation Institute for Medical Research

Xingjie Ma

Centre de Recherche en Cancérologie de Lyon

Eyra Marien

KU Leuven

Jonas Dehairs

KU Leuven

Julie Neveu

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

Romain Le Bars

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

Johannes Swinnen

KU Leuven

David Bernard

Centre de Recherche en Cancérologie de Lyon

David Tareste

Universite Paris Descartes

Vesa M. Olkkonen

Minerva Foundation Institute for Medical Research

Francesca Giordano

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

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Abstract

Mitochondria are dynamic organelles essential for cell survival whose structural and functional integrity rely on selective and regulated transport of lipids from/to the endoplasmic reticulum (ER) and across the two mitochondrial membranes. As they are not connected by vesicle transport, the exchange of lipids between ER and mitochondria occurs at sites of close organelle apposition called membrane contact sites. However, the mechanisms and proteins involved in these processes are only beginning to emerge. Here, we show that ORP5/8 mediate non-vesicular transport of Phosphatidylserine (PS) from the ER to mitochondria in mammalian cells. We also show that ER-mitochondria contacts where ORP5/8 reside are physically and functionally linked to the MIB/MICOS complexes that bridge the mitochondria membranes, cooperating with them to facilitate PS transfer from the ER to the mitochondria. Finally, we show that ORP5 but not ORP8, additionally regulates import of calcium to mitochondria and consequently cell senescence.

Keywords: Membrane contact sites, Mitochondria, ORP, Lipid transfer, Calcium

Suggested Citation

Rochin, Leila and Sauvanet, Cécile and Jääskeläinen, Eeva and Houcine, Audrey and Kivela, Annukka and Ma, Xingjie and Marien, Eyra and Dehairs, Jonas and Neveu, Julie and Le Bars, Romain and Swinnen, Johannes and Bernard, David and Tareste, David and Olkkonen, Vesa M. and Giordano, Francesca, ORP5 Transfers Phosphatidylserine to Mitochondria and Regulates Mitochondrial Calcium Uptake at Endoplasmic Reticulum - Mitochondria Contact Sites (September 6, 2019). DEVELOPMENTAL-CELL-D-19-00758. Available at SSRN: https://ssrn.com/abstract=3449275 or http://dx.doi.org/10.2139/ssrn.3449275
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Leila Rochin

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

55 Avenue de Paris
Versailles, 78000
France

Cécile Sauvanet

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

55 Avenue de Paris
Versailles, 78000
France

Eeva Jääskeläinen

Minerva Foundation Institute for Medical Research

Helsinki
Finland

Audrey Houcine

Université Paris VII Denis Diderot - IJM - Institut Jacques Monod

2, place Jussieu
Paris, 75005
France

Annukka Kivela

Minerva Foundation Institute for Medical Research

Helsinki
Finland

Xingjie Ma

Centre de Recherche en Cancérologie de Lyon

France

Eyra Marien

KU Leuven

Oude Markt 13
Leuven, Vlaams-Brabant 3000
Belgium

Jonas Dehairs

KU Leuven

Oude Markt 13
Leuven, Vlaams-Brabant 3000
Belgium

Julie Neveu

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

55 Avenue de Paris
Versailles, 78000
France

Romain Le Bars

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC)

55 Avenue de Paris
Versailles, 78000
France

Johannes Swinnen

KU Leuven

Oude Markt 13
Leuven, Vlaams-Brabant 3000
Belgium

David Bernard

Centre de Recherche en Cancérologie de Lyon

France

David Tareste

Universite Paris Descartes

12, rue de l'Ecole de Médecine
Cedex 06
Paris, 75270
France

Vesa M. Olkkonen

Minerva Foundation Institute for Medical Research

Helsinki
Finland

Francesca Giordano (Contact Author)

Université Paris Sud-Paris Saclay - Institute for Integrative Biology of the Cell (I2BC) ( email )

55 Avenue de Paris
Versailles, 78000
France

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