Sem1, 26S proteasome degradation and cellular redox state

Miriam Kolog Gulko 1,4 Gabriele Heinrich 1,4 Carina Gross 1,4 Blagovesta Popova 1,3,4 Oliver Valerius 1,4 Piotr Neumann 2,4 Ralf Ficner 2,4 Gerhard H. Braus 1,4
1Molecular Microbiology and Genetics, Georg August University Göttingen, Göttingen, Germany
2Department of Structural Biology, Georg-August-University, Göttingen, Germany
3Center for Nanoscale Microscopy and Molecular Physiology of Brain (CNMPB, Georg-August-University, Göttingen, Germany
4Göttingen Center for Molecular Biosciences (GZMB), Georg-August-University, Göttingen, Germany

Sem1 is bona fide lid subunit of the proteasome. The role of this intrinsically disordered protein was investigated in the multicellular model organism Aspergillus nidulans as the human corresponding gene is essential. We found that Sem1 from A. nidulans is required for oxidative stress response, mitochondria integrity and proteasome assembly. Sem1 is not required for vegetative fungal growth but it is essential for cellular differentiation and coordination of secondary metabolites. Oxidative stress response in the wild type included increased transcriptional levels of detoxificating enzymes and proteasomal subunits semA and rpn11, whereas the mutant strain exhibited damaged and dysfunctional mitochondria. EM revealed increased number of 20S proteasomes in ΔsemA mutant strain with double the catalytic activity compared to the complementation strain. This enhanced degradation rate of 20S proteasome presumably serve the purpose of dealing with accumulation of damaged proteins due to oxidative stress.