Kim S-Y, Zhang Q, Brunmeir R, Han W, Xu F (2015) SIRT1 Interacts with and Deacetylates ATP6V1B2 in Mature Adipocytes. PLoS ONE 10(7): e0133448. doi:10.1371/journal.pone.0133448
SIRT1 plays a key role in maintaining metabolic homeostasis in mammals by directly modulating the activities of various transcription factors and metabolic enzymes through lysine deacetylation. White adipose tissue plays a key role in lipid storage and metabolism. To identify novel molecular targets of SIRT1 in fat cells, we used a non-biased proteomic approach. We identified a number of proteins whose acetylation status was significantly affected by SIRT1 modulator treatment in 3T3-L1 adipocytes. Among them, ATP6V1B2, a subunit of the vacuolar (H+)-ATPase, was further shown to be associated with SIRT1 by co-immunoprecipitation assay. Moreover, SIRT1 deacetylates ATP6V1B2 in vitro and in vivo. Taken together, our study demonstrates that ATP6V1B2 is a molecular target of SIRT1 in fat cells and the role of SIRT1 and ATP6V1B2 acetylation in the vacuolar (H+)-ATPase function warrants further investigation.
This work was supported by the Academic Center of Excellence Research Grant (No. 100019545) from GSK and the Industry Alignment Fund (IAF111002) from the Agency for Science, Technology and Research (A*STAR) of Singapore to F.X. Funding for the open-access charge was provided by A*STAR of Singapore. GSK provided the SIRT1 modulators for this study and performed the non-biased proteomic analysis to identify novel SIRT1 targets. Other than that, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.