Riboflavin transporter SLC52A1, a target of p53, suppresses cellular senescence by activating mitochondrial complex II
Taiki Nagano, Yuto Awai, Shione Kuwaba, Taiichi Osumi, Kentaro Mio, Tetsushi Iwasaki, Shinji Kamada
Abstract
promoted senescence phenotypes induced by DNA damage in tumor and normal cells. The senescence suppressive action of SLC52A1 was dependent on its riboflavin transport activity. Furthermore, elevation of intracellular riboflavin led to activation of mitochondrial membrane potential (MMP) mediated by the mitochondrial electron transport chain complex II. Finally, the SLC52A1-dependent activation of MMP inhibited the AMPK-p53 pathway, a central mediator of mitochondria dysfunction-related senescence. These results suggest that SLC52A1 contributes to suppress senescence through the uptake of riboflavin and acts downstream of p53 as a negative feedback mechanism to limit aberrant senescence induction.