NADH Binds and Stabilizes the 26S Proteasomes Independent of ATP

Peter Tsvetkov, Nadav Myers, Raz Eliav, Yaarit Adamovich, Tzachi Hagai, Julia Adler, Ami Navon, Yosef Shaul

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים


Background: 26S proteasome complex is highly dependent on ATP. Results: NADH binds the proteasome via the Psmc1 subunit resulting in ATP-independent stabilization of the 26S proteasome complex, in vitro and in cells. Conclusion: NADH is a novel regulator of the 26S proteasome. Significance: NADH can maintain proteasomal integrity in the absence of ATP, linking cellular redox state to protein degradation. 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 GxGxxG 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.
שפה מקוריתאנגלית
עמודים (מ-עד)11272-11281
מספר עמודים10
כתב עתJournal of Biological Chemistry
מספר גיליון16
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - 18 אפר׳ 2014

ASJC Scopus subject areas

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