Pls1 Is a Peroxisomal Matrix Protein with a Role in Regulating Lysine Biosynthesis

Yotam David, Inês Gomes Castro, Eden Yifrach, Chen Bibi, Enas Katawi, Dekel Yahav Har-Shai, Sagie Brodsky, Naama Barkai, Tommer Ravid, Miriam Eisenstein, Shmuel Pietrokovski, Maya Schuldiner*, Einat Zalckvar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Peroxisomes host essential metabolic enzymes and are crucial for human health and survival. Although peroxisomes were first described over 60 years ago, their entire proteome has not yet been identified. As a basis for understanding the variety of peroxisomal functions, we used a high-throughput screen to discover peroxisomal proteins in yeast. To visualize low abundance proteins, we utilized a collection of strains containing a peroxisomal marker in which each protein is expressed from the constitutive and strong TEF2 promoter. Using this approach, we uncovered 18 proteins that were not observed in peroxisomes before and could show their metabolic and targeting factor dependence for peroxisomal localization. We focus on one newly identified and uncharacterized matrix protein, Ynl097c-b, and show that it localizes to peroxisomes upon lysine deprivation and that its localization to peroxisomes depends on the lysine biosynthesis enzyme, Lys1. We demonstrate that Ynl097c-b affects the abundance of Lys1 and the lysine biosynthesis pathway. We have therefore renamed this protein Pls1 for Peroxisomal Lys1 Stabilizing 1. Our work uncovers an additional layer of regulation on the central lysine biosynthesis pathway. More generally it highlights how the discovery of peroxisomal proteins can expand our understanding of cellular metabolism.

Original languageAmerican English
Article number1426
JournalCells
Volume11
Issue number9
DOIs
StatePublished - 1 May 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Lys1
  • Pex5
  • Saccharomyces cerevisiae
  • high-content screen
  • lysine
  • peroxisome
  • protein targeting
  • saccharopine

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