Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway
The ubiquitin-like protein NEDD8/Rub1 is initially translated as a precursor and undergoes maturation before becoming functional, a process mediated by the ubiquitin hydrolase UCHL3/Yuh1. Across studied organisms, the mature form of NEDD8/Rub1 modifies cullins, the central subunits of CRLs. NEDD8/Ru...
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Elsevier
2025-06-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231725001685 |
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| author | Soha Issa Yuval Klein Eden Berda Shahaf Saad Yehonatan Sharaby Moran Benhar Elah Pick |
| author_facet | Soha Issa Yuval Klein Eden Berda Shahaf Saad Yehonatan Sharaby Moran Benhar Elah Pick |
| author_sort | Soha Issa |
| collection | DOAJ |
| description | The ubiquitin-like protein NEDD8/Rub1 is initially translated as a precursor and undergoes maturation before becoming functional, a process mediated by the ubiquitin hydrolase UCHL3/Yuh1. Across studied organisms, the mature form of NEDD8/Rub1 modifies cullins, the central subunits of CRLs. NEDD8/Rub1 modification typically enhances CRL-mediated ubiquitination of key cellular regulators, leading to their proteasomal degradation. However, in S. cerevisiae, cullin modification by NEDD8/Rub1 occurs but does not regulate substrate turnover, prompting the question of whether NEDD8/Rub1 has a conserved role beyond CRL activation.Previous studies in S. cerevisiae have shown that increased production of reactive oxygen species (ROS) during the diauxic shift, a transition from glycolysis to mitochondrial respiration, inhibits cullin NEDDylation, though the specific enzymes affected remain unidentified. Here, we investigated how changes in the redox state affect Yuh1 catalytic function. Our findings reveal a thiol-based redox switch that modulates Yuh1 catalytic function in response to accumulated ROS. Our results suggest that the fine-tuning between the mature and precursor forms of NEDD8/Rub1 through temporal inactivation of Yuh1 is essential for maintaining mitochondrial integrity and enhancing resilience to oxidative stress. These results unveil a novel role for CRL-free NEDD8/Rub1 in redox signaling. |
| format | Article |
| id | doaj-art-00b9b5462e95477eb35b07976196f9a4 |
| institution | DOAJ |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-00b9b5462e95477eb35b07976196f9a42025-08-20T03:10:25ZengElsevierRedox Biology2213-23172025-06-018310365510.1016/j.redox.2025.103655Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathwaySoha Issa0Yuval Klein1Eden Berda2Shahaf Saad3Yehonatan Sharaby4Moran Benhar5Elah Pick6Department of Evolutionary and Environmental Biology, University of Haifa, Haifa, 3190500, IsraelDepartment of Human Biology, University of Haifa, Haifa, 31905, IsraelDepartment of Biology and Environment, University of Haifa at Oranim, Tivon, 3600600, IsraelDepartment of Biology and Environment, University of Haifa at Oranim, Tivon, 3600600, IsraelDepartment of Biology and Environment, University of Haifa at Oranim, Tivon, 3600600, IsraelDepartment of Biochemistry, Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Haifa, 3109601, IsraelDepartment of Evolutionary and Environmental Biology, University of Haifa, Haifa, 3190500, Israel; Department of Human Biology, University of Haifa, Haifa, 31905, Israel; Department of Biology and Environment, University of Haifa at Oranim, Tivon, 3600600, Israel; Corresponding author. Department of Evolutionary and Environmental Biology, University of Haifa, Haifa, 3190500, Israel.The ubiquitin-like protein NEDD8/Rub1 is initially translated as a precursor and undergoes maturation before becoming functional, a process mediated by the ubiquitin hydrolase UCHL3/Yuh1. Across studied organisms, the mature form of NEDD8/Rub1 modifies cullins, the central subunits of CRLs. NEDD8/Rub1 modification typically enhances CRL-mediated ubiquitination of key cellular regulators, leading to their proteasomal degradation. However, in S. cerevisiae, cullin modification by NEDD8/Rub1 occurs but does not regulate substrate turnover, prompting the question of whether NEDD8/Rub1 has a conserved role beyond CRL activation.Previous studies in S. cerevisiae have shown that increased production of reactive oxygen species (ROS) during the diauxic shift, a transition from glycolysis to mitochondrial respiration, inhibits cullin NEDDylation, though the specific enzymes affected remain unidentified. Here, we investigated how changes in the redox state affect Yuh1 catalytic function. Our findings reveal a thiol-based redox switch that modulates Yuh1 catalytic function in response to accumulated ROS. Our results suggest that the fine-tuning between the mature and precursor forms of NEDD8/Rub1 through temporal inactivation of Yuh1 is essential for maintaining mitochondrial integrity and enhancing resilience to oxidative stress. These results unveil a novel role for CRL-free NEDD8/Rub1 in redox signaling.http://www.sciencedirect.com/science/article/pii/S2213231725001685Reactive oxygen speciesNEDD8/Rub1UbiquitinCullin neddylationYuh1Redox regulation |
| spellingShingle | Soha Issa Yuval Klein Eden Berda Shahaf Saad Yehonatan Sharaby Moran Benhar Elah Pick Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway Redox Biology Reactive oxygen species NEDD8/Rub1 Ubiquitin Cullin neddylation Yuh1 Redox regulation |
| title | Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway |
| title_full | Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway |
| title_fullStr | Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway |
| title_full_unstemmed | Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway |
| title_short | Redox-driven regulation of UCHL3/Yuh1 influences mitochondrial health via the NEDD8/Rub1 pathway |
| title_sort | redox driven regulation of uchl3 yuh1 influences mitochondrial health via the nedd8 rub1 pathway |
| topic | Reactive oxygen species NEDD8/Rub1 Ubiquitin Cullin neddylation Yuh1 Redox regulation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231725001685 |
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