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: UNIPROT:P02794 (
ferritin
)
17,525
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Iron is vital for many homeostatic processes, and its liberation from
ferritin
nanocages occurs in the lysosome. Studies indicate that
ferritin
and its binding partner nuclear receptor coactivator-4 (NCOA4) are targeted to lysosomes by a form of selective autophagy. By using genome-scale functional screening, we identify an alternative lysosomal transport pathway for
ferritin
that requires FIP200, ATG9A, VPS34, and
TAX1BP1
but lacks involvement of the ATG8 lipidation machinery that constitutes classical macroautophagy.
TAX1BP1
binds directly to NCOA4 and is required for lysosomal trafficking of
ferritin
under basal and iron-depleted conditions. Under basal conditions ULK1/2-FIP200 controls
ferritin
turnover, but its deletion leads to
TAX1BP1
-dependent activation of TBK1 that regulates redistribution of ATG9A to the Golgi enabling continued trafficking of
ferritin
. Cells expressing an amyotrophic lateral sclerosis (ALS)-associated TBK1 allele are incapable of degrading
ferritin
suggesting a molecular mechanism that explains the presence of iron deposits in patient brain biopsies.
...
PMID:Autophagy-Independent Lysosomal Targeting Regulated by ULK1/2-FIP200 and ATG9. 2887 69
