Bioenergetics Reprogrammed in a Cellular Model of Friedreich's Ataxia: Frataxin Deficiency Affects Formation of Respiratory Supercomplexes and Down-regulates Both OXPHOS and Glycolysis.
Year: 2013
Type: article
Abstract: Friedreich's ataxia (FRDA) is an inherited progressive neuro- and cardio- degenerative disease that is caused by a reduced expression of the mitochondrial iron-binding protein, frataxin. FRDA is associated with decreased ATP level. This has been attributed to mitochondrial dysfunction as a result of frataxin deficiency, specifically decreased activities of respiratory complexes. In a stable human cell model of FRDA created by knocking down frataxin in LN428 using lentiviral shRNA, we found that glycolysis, as well as OXPHOS, was significantly down-regulated, leading to reduced steady-state ATP levels. In consistence, PCR array analysis revealed an overall down-regulation in genes involved in glucose metabolism. Meanwhile, the fatty acid oxidation was also reduced by frataxin deficiency. And blue native gel electrophoresis analysis indicated that frataxin deficiency affected assembly of respiratory complexes and formation of supercomplexes. We conclude that frataxin deficiency exerts far more complicated effects on energy metabolism than previously thought, and bioenergetics reprogramming plays an important role for the pathological development of Friedreich's ataxia.
Source: Europe PMC (PubMed Central)
Authors: Bennett Van Houten, Tao Wang
Institution: University of Pittsburgh
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2296025435