In:
Biological Chemistry, Walter de Gruyter GmbH, Vol. 404, No. 2-3 ( 2023-02-23), p. 135-155
Abstract:
Peroxisomes are organelles with vital functions in metabolism and their dysfunction is associated with human diseases. To fulfill their multiple roles, peroxisomes import nuclear-encoded matrix proteins, most carrying a peroxisomal targeting signal (PTS) 1. The receptor Pex5p recruits PTS1-proteins for import into peroxisomes; whether and how this process is posttranslationally regulated is unknown. Here, we identify 22 phosphorylation sites of Pex5p. Yeast cells expressing phospho-mimicking Pex5p-S507/523D (Pex5p 2D ) show decreased import of GFP with a PTS1. We show that the binding affinity between a PTS1-protein and Pex5p 2D is reduced. An in vivo analysis of the effect of the phospho-mimicking mutant on PTS1-proteins revealed that import of most, but not all, cargos is affected. The physiological effect of the phosphomimetic mutations correlates with the binding affinity of the corresponding extended PTS1-sequences. Thus, we report a novel Pex5p phosphorylation-dependent mechanism for regulating PTS1-protein import into peroxisomes. In a broader view, this suggests that posttranslational modifications can function in fine-tuning the peroxisomal protein composition and, thus, cellular metabolism.
Type of Medium:
Online Resource
ISSN:
1431-6730
,
1437-4315
DOI:
10.1515/hsz-2022-0168
Language:
English
Publisher:
Walter de Gruyter GmbH
Publication Date:
2023
detail.hit.zdb_id:
1466062-3
SSG:
12
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