Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.2 (
PDK1
)
2,238
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by mutations in
Frataxin
(
FXN
). Loss of
FXN
causes impaired mitochondrial function and iron homeostasis. An elevated production of reactive oxygen species (ROS) was previously proposed to contribute to the pathogenesis of FRDA. We recently showed that loss of
frataxin homolog
(
fh
), a
Drosophila
homolog of
FXN
, causes a ROS independent neurodegeneration in flies (Chen et al., 2016). In
fh
mutants, iron accumulation in the nervous system enhances the synthesis of sphingolipids, which in turn activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2) to trigger neurodegeneration of adult photoreceptors. Here, we show that loss of
Fxn
in the nervous system in mice also activates an iron/sphingolipid/
PDK1
/Mef2 pathway, indicating that the mechanism is evolutionarily conserved. Furthermore, sphingolipid levels and
PDK1
activity are also increased in hearts of FRDA patients, suggesting that a similar pathway is affected in FRDA.
...
PMID:Loss of Frataxin activates the iron/sphingolipid/PDK1/Mef2 pathway in mammals. 2790 68
