Περίληψη:
In an in silico search for correlated gene loss with fungal peroxisomal uric acid oxidase (UOX), we identified PMP22-like proteins, some of which function as promiscuous channels in organellar membranes. To investigate whether PMP22 channels have a role in peroxisomal uric acid transport and catabolism, we functionally analyzed the closest homologue in Aspergillus nidulans, named SspA. We confirmed that SspA is a peroxisomal membrane protein that co-localizes significantly with PTS1-tagged mRFP, UOX or HexA, the latter considered a protein of Woronin bodies (WB), organelles originating from peroxisomes that dynamically plug septal pores in ascomycetes. Our results suggest that in A. nidulans, unlike some other ascomycetes, there is no strict protein segregation of peroxisomal and WB-specific proteins. Importantly, genetic deletion of sspA, but not of hexA, led to lack of peroxisomal localization at septal pores, suggesting that SspA is a key factor for septal pore functioning. Additionally, ΔsspA resulted in increased sensitivity to oxidative stress, apparently as a consequence of not only the inability to plug septal pores, but also a recorded reduction in peroxisome biogenesis. However, deleting sspA had no effect on uric acid or purine utilization, as we hypothesized, a result also in line with the observation that expression of SspA was not affected by regulatory mutants and conditions known to control purine catabolic enzymes. Our results are discussed within the framework of previous studies of SspA homologues in other fungi, as well as, the observed gene losses of PMP22 and peroxisomal uric acid oxidase. © 2019 Elsevier Inc.
Συγγραφείς:
Dimou, S.
Kourkoulou, A.
Amillis, S.
Percudani, R.
Diallinas, G.
Λέξεις-κλειδιά:
HexA protein; membrane protein; peripheral myelin protein 22; PTS1 protein; SspA protein; unclassified drug; uric acid oxidase; Woronin body; fungal protein; membrane protein; purine derivative; uric acid, Article; Aspergillus nidulans; controlled study; fungus spore; gene deletion; gene interaction; gene knockout; gene loss; nonhuman; organelle biogenesis; oxidative stress; peroxisome; peroxisome biogenesis; priority journal; protein expression; protein localization; purine metabolism; genetics; metabolism, Aspergillus nidulans; Fungal Proteins; Gene Deletion; Membrane Proteins; Peroxisomes; Purines; Uric Acid
