ER-mitochondria contacts mediate lipid radical transfer via RMDN3/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress

The proximal domains of mitochondria and the endoplasmic reticulum (ER) are linked by tethering factors on each membrane, allowing the efficient transport 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 apply NanoBiT technology to develop the MERBiT system, which enables the measurement of reversible MERCs formation in living cells. Analysis using this system suggests that induction of mitochondrial ROS increases MERCs formation via RMDN3 (also known as PTPIP51)-VAPB tethering driven by RMDN3 phosphorylation. Disruption of this tethering caused lipid…

• JA
  Japan Agency for Medical Research and Development

  Awards: JP17gm5010002, JP18gm5010002, JP19gm5010002, JP20gm5010002, JP17gm5010002, JP19gm5010002, 23gm1610011h0001, JP18gm5010002, JP20gm5010002, JP19dm0207082
• KC
  Kowa Company
• MO
  Ministry of Education, Culture, Sports, Science and Technology

  Awards: 21H05267, JP18gm5010002
• KL
  Kowa Life Science Foundation
• JS
  Japan Society for the Promotion of Science

  Awards: 21H0207, 21H05267, 23K17979, 21K06844, 23H02691,20H04911,20H03454, 23K14185, 22K20637, 22H05532, 22K20637, 23K17979, 20H03454, 23K14185, 22K15399, 22H05574, 24H01327, 20H04911, 22K15399