PEROXISOMAL FATTY-ACID BETA-OXIDATION IN HEPG2 CELLS

HepG2 cells, originally derived from a human hepatoblastoma, contain peroxisomes which could be separated from mitochondria and other subcellular organelles by density gradient centrifugation. To determine whether this cell line was a suitable model for human peroxisomal fatty acid β-oxidation, we investigated the ability of these cells to catabolize very-long-chain fatty acids (VLCFA). HepG2 cell homogenates or digitonindisrupted cells oxidized both long chain fatty acids and VLCFA, although at somewhat lower rates than human liver homogenates. β-Oxidation of VLCFA was observed in both peroxisomes and mitochondria of HepG2 cells. Peroxisomal β-oxidation was independent of carnitine, insensitive to antimycin A and rotenone, and not blocked by an inhibitor of carnitine palmitoyl transferase I. HepG2 peroxisomes contained immunoreactive acyl-CoA oxidase, the first enzyme unique to the peroxisomal β-oxidation pathway. In addition, HepG2 peroxisomes contained VLCFA-CoA synthetase activity. These results suggest that HepG2 may be a useful model system for the study of human peroxisomal metabolic processes, including β-oxidation of fatty acids. © 1991.