PT  - JOURNAL ARTICLE
AU  - Vera F. Monteiro-Cardoso
AU  - Leila Rochin
AU  - Amita Arora
AU  - Audrey Houcine
AU  - Eeva Jääskeläinen
AU  - Annukka M. Kivelä
AU  - Cécile Sauvanet
AU  - Romain Le Bars
AU  - Eyra Marien
AU  - Jonas Dehairs
AU  - Julie Neveu
AU  - Naima El Khallouki
AU  - Elena Santonico
AU  - Johannes V. Swinnen
AU  - David Tareste
AU  - Vesa M. Olkkonen
AU  - Francesca Giordano
TI  - ORP5/8 AND MIB/MICOS LINK ER-MITOCHONDRIA AND INTRAMITOCHONDRIAL CONTACTS FOR NON-VESICULAR TRANSPORT OF PHOSPHATIDYLSERINE
AID  - 10.1101/695577
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 695577
4099  - http://biorxiv.org/content/early/2022/05/25/695577.short
4100  - http://biorxiv.org/content/early/2022/05/25/695577.full
AB  - 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 mitochondrial intermembrane space. As they are not connected by vesicular 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 the main physiological localization of the lipid transfer proteins ORP5 and ORP8 is at mitochondria-associated ER membranes (MAMs) subdomains, physically linked to the MIB/MICOS complexes that bridge the two mitochondrial membranes. We also show that ORP5/8 mediate non-vesicular transport of phosphatidylserine (PS) lipids from the ER to mitochondria by cooperating with the MIB/MICOS complexes. Overall our study reveals a novel physical and functional link between ER-mitochondria contacts involved in lipid transfer and intra-mitochondrial membranes contacts maintained by the MIB/MICOS complexes.Competing Interest StatementThe authors have declared no competing interest.