EVIDENCE THAT THE AMP-ACTIVATED PROTEIN-KINASE STIMULATES RAT-LIVER CARNITINE PALMITOYLTRANSFERASE-I BY PHOSPHORYLATING CYTOSKELETAL COMPONENTS

The activity of hepatic carnitine palmitoyltransferase I (CPT-I) may b e modulated by interactions with cytoskeletal components [Velasco et a l, (1998) J, Biol. Chem, 273, 21497-21504]. We have studied whether th e AMP-activated protein kinase (AMPK) is involved in this process. AMP K stimulated CPT-I in permeabilized hepatocytes but not in isolated li ver mitochondria. In addition, AMPK: abrogated the inhibition of CPT-I of isolated mitochondria induced by a cytoskeletal fraction. These tw o effects of AMPK were not evident when the kinase was inactivated by pretreatment with protein phosphatase 2C, Cytokeratins 8 and 18 were p hosphorylated by AMPK in vitro and by incubation of intact hepatocytes with 5-aminoimidazole-4-carboxamide ribonucleoside, a cell-permeable activator of AMPK. These results provide the first evidence that AMPK stimulates CPT-I by direct phosphorylation of cytoskeletal components. (C) 1998 Federation of European Biochemical Societies.