期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1863, 期 2, 页码 271-283出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2015.11.013
关键词
Membrane channels; beta-Oxidation; Peroxisomes; Protein phosphorylation; TRP channels
资金
- Academy of Finland
- Sigrid Juselius Foundation
- Deutsche Forschungsgemeinschaft [RE178/2-4]
More than 30 proteins (Pex proteins) are known to participate in the biogenesis of peroxisomes-ubiquitous oxidative organelles involved in lipid and ROS metabolism. The Pex11 family of homologous proteins is responsible for division and proliferation of peroxisomes. We show that yeast Pex11 is a pore-forming protein sharing sequence similarity with TRAM cation-selective channels. The Pex11 channel with a conductance of A = 4.1 nS in 1.0 M KCl is moderately cation-selective (PK+/P-Cl- = 1.85) and resistant to voltage-dependent closing. The estimated size of the channel's pore (r similar to 0.6 nm) supports the notion that Pex11 conducts solutes with molecular mass below 300-400 Da. We localized the channel's selectivity determining sequence. Overexpression of Pex11 resulted in acceleration of fatty acids beta-oxidation in intact cells but not in the corresponding lysates. The beta-oxidation was affected in cells by expression of the Pex11 protein carrying point mutations in the selectivity determining sequence. These data suggest that the Pex11-dependent transmembrane traffic of metabolites may be a rate-limiting step in the beta-oxidation of fatty acids. This conclusion was corroborated by analysis of the rate of beta-oxidation in yeast strains expressing Pex11 with mutations mimicking constitutively phosphotylated (S165D, S167D) or unphosphorylated (S165A, S167A) protein. The results suggest that phosphorylation of Pex11 is a mechanism that can control the peroxisomal beta-oxidation rate. Our results disclose an unexpected function of Pex11 as a non-selective channel responsible for transfer of metabolites across peroxisomal membrane. The data indicate that peroxins may be involved in peroxisomal metabolic processes in addition to their role in peroxisome biogenesis. (C) 2015 Elsevier B.V. All rights reserved.
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