Phospholipid transfer function of PTPIP51 at mitochondria-associated ER membranes

Hyun Ku Yeo, Tae Hyun Park, Hee Yeon Kim, Hyonchol Jang, Jueun Lee, Geum Sook Hwang, Seong Eon Ryu, Si Hoon Park, Hyun Kyu Song, Hyun Seung Ban, Hye Jin Yoon, Byung Il Lee

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)


In eukaryotic cells, mitochondria are closely tethered to the endoplasmic reticulum (ER) at sites called mitochondria-associated ER membranes (MAMs). Ca2+ ion and phospholipid transfer occurs at MAMs to support diverse cellular functions. Unlike those in yeast, the protein complexes involved in phospholipid transfer at MAMs in humans have not been identified. Here, we determine the crystal structure of the tetratricopeptide repeat domain of PTPIP51 (PTPIP51_TPR), a mitochondrial protein that interacts with the ER-anchored VAPB protein at MAMs. The structure of PTPIP51_TPR shows an archetypal TPR fold, and an electron density map corresponding to an unidentified lipid-like molecule probably derived from the protein expression host is found in the structure. We reveal functions of PTPIP51 in phospholipid binding/transfer, particularly of phosphatidic acid, in vitro. Depletion of PTPIP51 in cells reduces the mitochondrial cardiolipin level. Additionally, we confirm that the PTPIP51–VAPB interaction is mediated by the FFAT-like motif of PTPIP51 and the MSP domain of VAPB. Our findings suggest that PTPIP51 is a phospholipid transfer protein with a MAM-tethering function.

Original languageEnglish
Article numbere51323
JournalEMBO Reports
Issue number6
Publication statusPublished - 2021 Jun 4

Bibliographical note

Publisher Copyright:
© 2021 The Authors


  • MAM
  • PTPIP51
  • endoplasmic reticulum
  • mitochondria
  • phospholipid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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