Metabolomic alterations in myeloma cells as a result of CLPP inhibition or inducible knockdown impair ATP production. (A) Global metabolic profiles in MM1.S cells with pharmacologic inhibition (left [50 μM] and middle [250 μM]) or inducible knockdown (right) of CLPP. Venn diagrams showing the numbers of upregulated (B) or downregulated metabolites (C) in MM1.S cells exposed to the 2 different A2-32-01 concentrations for 12, 24, and 48 hours and the number of overlapping metabolites. Heat maps showing alteration of metabolites involved in glycolysis (D), the TCA cycle and redox metabolism (E), and the PPP (F), as a result of pharmacologic inhibition (upper panel) or knockdown (lower or right panels). shCLPP, CLPP shRNA; shCtrl, nontargeting control shRNA.