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NADH Binds and Stabilizes the 26S Proteasomes Independent of ATP |
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| Authors: | Peter Tsvetkov Nadav Myers Raz Eliav Yaarit Adamovich Tzachi Hagai Julia Adler Ami Navon Yosef Shaul |
| Institution: | From the Departments of ‡Molecular Genetics and ;¶Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel and ;§Department Microbiology and Immunology, University of California, San Francisco School of Medicine, San Francisco, California 94158 |
| Abstract: | The 26S proteasome is the end point of the ubiquitin- and ATP-dependent degradation pathway. The 26S proteasome complex (26S PC) integrity and function has been shown to be highly dependent on ATP and its homolog nucleotides. We report here that the redox molecule NADH binds the 26S PC and is sufficient in maintaining 26S PC integrity even in the absence of ATP. Five of the 19S proteasome complex subunits contain a putative NADH binding motif (GxGxxG) including the AAA-ATPase subunit, Psmc1 (Rpt2). We demonstrate that recombinant Psmc1 binds NADH via the GxGxxG motif. Introducing the ΔGxGxxG Psmc1 mutant into cells results in reduced NADH-stabilized 26S proteasomes and decreased viability following redox stress induced by the mitochondrial inhibitor rotenone. The newly identified NADH binding of 26S proteasomes advances our understanding of the molecular mechanisms of protein degradation and highlights a new link between protein homeostasis and the cellular metabolic/redox state. |
| Keywords: | ATP-dependent Protease ATPases Magnesium NADH Proteasome Protein Degradation Psmc1 Rotenone |