Proteins that carry dual targeting signals can act as tethers between peroxisomes and partner organelles

PLoS Biol. 2024 Feb 20;22(2):e3002508. doi: 10.1371/journal.pbio.3002508. eCollection 2024 Feb.

Abstract

Peroxisomes are organelles with crucial functions in oxidative metabolism. To correctly target to peroxisomes, proteins require specialized targeting signals. A mystery in the field is the sorting of proteins that carry a targeting signal for peroxisomes and as well as for other organelles, such as mitochondria or the endoplasmic reticulum (ER). Exploring several of these proteins in fungal model systems, we observed that they can act as tethers bridging organelles together to create contact sites. We show that in Saccharomyces cerevisiae this mode of tethering involves the peroxisome import machinery, the ER-mitochondria encounter structure (ERMES) at mitochondria and the guided entry of tail-anchored proteins (GET) pathway at the ER. Our findings introduce a previously unexplored concept of how dual affinity proteins can regulate organelle attachment and communication.

MeSH terms

  • Cell Movement
  • Cell Respiration
  • Endoplasmic Reticulum
  • Mitochondria*
  • Peroxisomes*
  • Saccharomyces cerevisiae

Grants and funding

TS received funding from a fellowship from DAAD (https://www.daad.de/de/). GB thanks the European Research Council (ERC) for support through the project “KIWIsome” (Grant agreement number: 101019765). The project in the Schuldiner laboratory was supported by funding from ERC under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 864068). The robotic system of the Schuldiner laboratory was purchased through the support of the Blythe Brenden-Mann Foundation. MS is an Incumbent of the Dr. Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics. RS is an investigator of the Howard Hughes Medical Institute. JF was supported by a fellowship from Leopoldina and by the German research foundation (FR 3586/2-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.