ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress by Isshin Shiiba1 , Naoki Ito 1, Hijiri Oshio1, Yuto Ishikawa1, Takahiro Nagao2, ISBN 101038/S41467025566664 instant download

ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress by Isshin Shiiba1 , Naoki Ito 1, Hijiri Oshio1, Yuto Ishikawa1, Takahiro Nagao2, ISBN 101038/S41467025566664 instant download

The proximal domains of mitochondria and the endoplasmic reticulum (ER)are linked by tethering factors on each membrane, allowing the efficienttransport of substances, including lipids and calcium, between them. However,little is known about the regulation and function of mitochondria-ER contacts(MERCs) dynamics under mitochondrial damage. In this study, we applyNanoBiT technology to develop the MERBiT system, which enables the measurement of reversible MERCs formation in living cells. Analysis using thissystem suggests that induction of mitochondrial ROS increases MERCs formation via RMDN3 (also known as PTPIP51)-VAPB tethering driven by RMDN3phosphorylation. Disruption of this tethering caused lipid radical accumulation in mitochondria, leading to cell death. The lipid radical transfer activity ofthe TPR domain in RMDN3, as revealed by an in vitro liposome assay, suggeststhat RMDN3 transfers lipid radicals from mitochondria to the ER. Our findingssuggest a potential role for MERCs in cell survival strategy by facilitating theremoval of mitochondrial lipid radicals under mitochondrial damage.