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Journal articles
Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts
Abstract : Abstract Friedreich ataxia (FRDA) is a frequent autosomal recessive disease caused by a GAA repeat expansion in the FXN gene encoding frataxin, a mitochondrial protein involved in iron-sulfur cluster (ISC) biogenesis. Resulting frataxin deficiency affects ISC-containing proteins and causes iron to accumulate in the brain and heart of FRDA patients. Here we report on abnormal cellular iron homeostasis in FRDA fibroblasts inducing a massive iron overload in cytosol and mitochondria. We observe membrane transferrin receptor 1 (TfR1) accumulation, increased TfR1 endocytosis, and delayed Tf recycling, ascribing this to impaired TfR1 palmitoylation. Frataxin deficiency is shown to reduce coenzyme A (CoA) availability for TfR1 palmitoylation. Finally, we demonstrate that artesunate, CoA, and dichloroacetate improve TfR1 palmitoylation and decrease iron overload, paving the road for evidence-based therapeutic strategies at the actionable level of TfR1 palmitoylation in FRDA.
https://hal-univ-paris.archives-ouvertes.fr/hal-03241848
Contributor : Hal Paris Diderot <>
Submitted on : Saturday, May 29, 2021 - 12:21:42 PM
Last modification on : Wednesday, June 2, 2021 - 4:27:36 PM
Contributor : Hal Paris Diderot <>
Submitted on : Saturday, May 29, 2021 - 12:21:42 PM
Last modification on : Wednesday, June 2, 2021 - 4:27:36 PM