US EPA

1038232 

Journal Article 

Phosphorylation-dependent Pex11p and Fis1p interaction regulates peroxisome division 

Joshi, S; Agrawal, G; Subramani, S 

2012 

1 

Molecular Biology of the Cell
ISSN: 1059-1524
EISSN: 1939-4586 

23 

7 

1307-1315 

English 

22337771 

10.1091/mbc.E11-09-0782 

Peroxisome division is regulated by the conserved peroxin Pex11p. In Saccharomyces cerevisiae, induction of the phosphoprotein, ScPex11p, coincides with peroxisome biogenesis. We show that the ScPex11p homolog in Pichia pastoris (PpPex11p) is phosphorylated at Serine(173). PpPex11p expression and phosphorylation are induced in oleate and coordinated with peroxisome biogenesis. PpPex11p transits to peroxisomes via the endoplasmic reticulum (ER). PpPex11p is unstable and ER-restricted in pex3Δ and pex19Δ cells, which are impaired in peroxisomal membrane protein biogenesis. In oleate medium, the P. pastoris mutants, pex11A (constitutively unphosphorylated - S173A) and pex11D (constitutively phosphorylated - S173D), exhibit juxtaposed elongated peroxisomes (JEPs) and hyper-divided forms respectively, although protein levels remain unchanged. In contrast with ScPex11p, the ER to peroxisome translocation in P. pastoris is phosphorylation-independent and the phosphorylation occurs at the peroxisome. Neither PpPex11p nor PpFis1p are necessary for peroxisome division in methanol medium. We show that PpPex11p interacts with the peroxisome fission machinery via PpFis1p and is regulated by phosphorylation because PpPex11p and PpPex11Dp interact more strongly with PpFis1p, as compared with PpPex11Ap. We propose a model for the role of PpPex11p in the regulation of peroxisome division through a phosphorylation-dependent interaction with the fission machinery, providing novel insights into peroxisome morphogenesis.