PTPIP51

PTPIP51, or Protein Tyrosine Phosphatase Interacting Protein 51, is a mitochondrial outer membrane protein encoded in humans by the PTPIP1 gene. It localizes to the outer mitochondrial membrane and participates in the formation of contact sites between the endoplasmic reticulum and mitochondria, collectively known as mitochondria-associated membranes (MAMs).

PTPIP51 functions as a component of ER–mitochondria tethering by binding to VAPB, an ER-resident protein. Through this interaction, PTPIP51 contributes to the physical linkage between the two organelles, facilitating calcium transfer from the ER to mitochondria and influencing mitochondrial metabolism and energy production. Its activity as a tether is subject to regulation by phosphorylation, with signaling pathways that modify the phosphorylation state of PTPIP51 capable of altering ER–mitochondria contacts and calcium flux.

In terms of significance, proper ER–mitochondria contact is essential for calcium signaling, lipid exchange, and mitochondrial function. Dysregulation of these contacts has been implicated in various diseases, including neurodegenerative disorders, though the particular contribution of PTPIP51 remains an area of ongoing research.

Structurally, PTPIP51 is a relatively small protein anchored to the mitochondrial outer membrane and is predicted to contain coiled-coil domains that promote protein–protein interactions. It is conserved across vertebrates, underscoring its role in fundamental cellular processes.

See also: ER–mitochondria contact sites (MAMs), VAPB, calcium signaling, PTP1B.