AMP‐activated protein kinase (AMPK) activity in Leigh Syndrome French Canadian Type (LSFC) patient fibroblasts: differences between primary and immortalized cell lines

Background & Objective LSFC is an autosomal recessive disease caused by mutations in the leucine‐rich pentatricopeptide repeat containing protein (LRPPRC) gene resulting in decreased LRPPRC expression. This leads to a tissue‐specific cytochrome c oxidase deficiency and a reduction in energy production. AMPK is a key enzyme in the regulation of energy homeostasis. To test the hypothesis that AMPK activity may differ in LSFC and control cells, we evaluated the phosphorylated and active form of AMPK in primary (P) fibroblasts and, because of the limited availability of P cells, we also tested their immortalized (I) counterparts. Results Under basal conditions, P fibroblasts from LSFC patients and controls showed marginal differences in the levels of phosphorylated AMPK (pAMPK) as well as acetyl‐CoA carboxylase (ACC), one of many AMPK substrates. However, compared to P cells, I cells from both controls and LSFC patients showed a 60% and 80% decrease in pAMPK, respectively. Consistent with pAMPK levels, phosphorylated ACC levels were also decreased in I cells by 58 % in controls and 69% in LSFC patients. The total levels of these proteins were similar in all cases. Conclusion These results highlight an important decrease in AMPK activity level in I vs. P cells, which may compromise the capacity of these cells to palliate an energy deficit. Supported by: Association de l'acidose lactique and CIHR Emerging Team Grant