biostudies-literatureWang CNCI NIH HHS26742-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC2785362biostudies-literatureUnknown284(39)Aldo-keto reductase family 1 member B10 (AKR1B10) is primarily expressed in the normal human colon and small intestine but overexpressed in liver and lung cancer. Our previous studies have shown that AKR1B10 mediates the ubiquitin-dependent degradation of acetyl-CoA carboxylase-alpha. In this study, we demonstrate that AKR1B10 is critical to cell survival. In human colon carcinoma cells (HCT-8) and lung carcinoma cells (NCI-H460), small-interfering RNA-induced AKR1B10 silencing resulted in caspase-3-mediated apoptosis. In these cells, the total and subspecies of cellular lipids, particularly of phospholipids, were decreased by more than 50%, concomitant with 2-3-fold increase in reactive oxygen species, mitochondrial cytochrome c efflux, and caspase-3 cleavage. AKR1B10 silencing also increThe Journal of biological chemistryAldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls.PMC2785362R21 CA122327R21 CA122622CA122622CA122327Wang CLiao DFCao DYan RWatabe KLuo DfalseAldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls.Aldo-keto reductase family 1 member B10 (AKR1B10) is primarily expressed in the normal human colon and small intestine but overexpressed in liver and lung cancer. Our previous studies have shown that AKR1B10 mediates the ubiquitin-dependent degradation of acetyl-CoA carboxylase-alpha. In this study, we demonstrate that AKR1B10 is critical to cell survival. In human colon carcinoma cells (HCT-8) and lung carcinoma cells (NCI-H460), small-interfering RNA-induced AKR1B10 silencing resulted in caspase-3-mediated apoptosis. In these cells, the total and subspecies of cellular lipids, particularly of phospholipids, were decreased by more than 50%, concomitant with 2-3-fold increase in reactive oxygen species, mitochondrial cytochrome c efflux, and caspase-3 cleavage. AKR1B10 silencing also incre2009-01-01T00:00:00Z2009 Sep2025-04-19T01:28:00.012Z2019-03-27T00:26:59ZS-EPMC27853621964372810.1074/jbc.M109.02289710.1074/jbc.m109.022897