Iron-induced cytotoxicity mediated by endolysosomal TRPML1 channels is reverted by TFEB.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
16 12 2022
16 12 2022
Historique:
received:
19
10
2022
accepted:
07
12
2022
revised:
30
11
2022
entrez:
15
12
2022
pubmed:
16
12
2022
medline:
20
12
2022
Statut:
epublish
Résumé
Increased brain iron content has been consistently reported in sporadic Parkinson's disease (PD) patients, and an increase in cytosolic free iron is known to cause oxidative stress and cell death. However, whether iron also accumulates in susceptible brain areas in humans or in mouse models of familial PD remains unknown. In addition, whilst the lysosome functions as a critical intracellular iron storage organelle, little is known about the mechanisms underlying lysosomal iron release and how this process is influenced by lysosome biogenesis and/or lysosomal exocytosis. Here, we report an increase in brain iron content also in PD patients due to the common G2019S-LRRK2 mutation as compared to healthy age-matched controls, whilst differences in iron content are not observed in G2019S-LRRK2 knockin as compared to control mice. Chemically triggering iron overload in cultured cells causes cytotoxicity via the endolysosomal release of iron which is mediated by TRPML1. TFEB expression reverts the iron overload-associated cytotoxicity by causing lysosomal exocytosis, which is dependent on a TRPML1-mediated increase in cytosolic calcium levels. Therefore, approaches aimed at increasing TFEB levels, or pharmacological TRPML1 activation in conjunction with iron chelation may prove beneficial against cell death associated with iron overload conditions such as those associated with PD.
Identifiants
pubmed: 36522443
doi: 10.1038/s41419-022-05504-2
pii: 10.1038/s41419-022-05504-2
pmc: PMC9755144
doi:
Substances chimiques
Iron
E1UOL152H7
Transient Receptor Potential Channels
0
Calcium
SY7Q814VUP
TFEB protein, human
0
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1047Informations de copyright
© 2022. The Author(s).
Références
J Neurophysiol. 2020 Jun 1;123(6):2382-2389
pubmed: 32374202
J Neural Transm (Vienna). 2022 Jun;129(5-6):505-520
pubmed: 35534717
Cell. 2013 Feb 14;152(4):778-790
pubmed: 23394946
Sci Signal. 2008 Nov 04;1(44):re10
pubmed: 18984909
Hum Mol Genet. 2019 Nov 1;28(21):3552-3568
pubmed: 31428781
Elife. 2022 Jan 11;11:
pubmed: 35014607
Cell Calcium. 2015 Jul;58(1):48-56
pubmed: 25465891
Prog Neurobiol. 2017 Aug;155:96-119
pubmed: 26455458
J Neurosci. 2016 Jul 6;36(27):7128-41
pubmed: 27383589
Neurobiol Dis. 2015 Jun;78:172-95
pubmed: 25836420
J Trace Elem Med Biol. 2014 Jan;28(1):1-7
pubmed: 24188895
Hum Mol Genet. 2019 Aug 15;28(16):2696-2710
pubmed: 31039583
J Biol Chem. 1969 Nov 25;244(22):6049-55
pubmed: 5389100
Brain Res. 2007 Aug 20;1164:24-31
pubmed: 17640623
Am J Physiol Cell Physiol. 2011 Aug;301(2):C421-30
pubmed: 21613607
Mov Disord. 2020 Apr;35(4):662-671
pubmed: 31889341
JCI Insight. 2019 Aug 22;4(16):
pubmed: 31434803
Cell Rep. 2015 Sep 1;12(9):1430-44
pubmed: 26299959
Neurobiol Aging. 2014 Apr;35(4):858-66
pubmed: 24176624
Science. 2009 Jul 24;325(5939):473-7
pubmed: 19556463
Pharmacol Ther. 2021 Apr;220:107713
pubmed: 33141027
Nat Cell Biol. 2016 Apr;18(4):404-17
pubmed: 26950892
Biochem Pharmacol. 1998 Feb 1;55(3):287-95
pubmed: 9484794
Sci Signal. 2012 Jun 12;5(228):ra42
pubmed: 22692423
Mov Disord. 2019 Oct;34(10):1440-1451
pubmed: 31251435
Neurobiol Dis. 2008 Apr;30(1):65-73
pubmed: 18243716
Cell Death Dis. 2020 Feb 18;11(2):128
pubmed: 32071296
J Neurosci. 2018 Nov 7;38(45):9700-9711
pubmed: 30249796
Biomolecules. 2020 Jan 29;10(2):
pubmed: 32013126
Kidney Int. 2016 Apr;89(4):862-73
pubmed: 26994576
Anal Biochem. 2004 Aug 15;331(2):370-5
pubmed: 15265744
Cells. 2022 Mar 21;11(6):
pubmed: 35326505
Cell Calcium. 2008 Jun;43(6):531-8
pubmed: 17935780
Neurology. 1998 Aug;51(2):565-9
pubmed: 9710036
Front Aging Neurosci. 2021 Mar 03;13:641222
pubmed: 33746735
Nat Commun. 2012 Mar 13;3:731
pubmed: 22415822
Exp Gerontol. 2009 Sep;44(9):594-600
pubmed: 19563877
Metallomics. 2016 Sep 1;8(9):853-62
pubmed: 27339113
Free Radic Biol Med. 1993 Jul;15(1):1-11
pubmed: 8359707
J Biol Chem. 2007 Aug 31;282(35):25259-69
pubmed: 17613490
Dev Cell. 2011 Sep 13;21(3):421-30
pubmed: 21889421
Front Chem. 2019 Mar 05;7:115
pubmed: 30891444
Handb Exp Pharmacol. 2022 Jul 26;:
pubmed: 35879580
PLoS Biol. 2021 Dec 16;19(12):e3001480
pubmed: 34914695
Neuron. 2004 Nov 18;44(4):601-7
pubmed: 15541309
Nat Rev Immunol. 2022 Nov;22(11):657-673
pubmed: 35246670
Cell. 2012 Oct 12;151(2):372-83
pubmed: 23063126
Autophagy. 2016 Sep;12(9):1487-506
pubmed: 27383256
Nat Rev Neurosci. 2013 Aug;14(8):551-64
pubmed: 23820773
Mol Ther. 2018 Jun 6;26(6):1552-1567
pubmed: 29628303
Cell Mol Life Sci. 2003 Aug;60(8):1733-43
pubmed: 14513838
Nat Cell Biol. 2015 Mar;17(3):288-99
pubmed: 25720963
Mov Disord. 2015 Jul;30(8):1077-84
pubmed: 26011561
J Biol Chem. 2010 Nov 5;285(45):34304-8
pubmed: 20864526
J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):418-425
pubmed: 32079673
Dis Model Mech. 2015 Dec;8(12):1591-601
pubmed: 26398942
Future Med Chem. 2010 Jan;2(1):51-64
pubmed: 20161623
Nat Commun. 2014 Aug 14;5:4681
pubmed: 25119295
Nature. 2008 Oct 16;455(7215):992-6
pubmed: 18794901
J Neurol. 2007 May;254(5):613-6
pubmed: 17415511
J Parkinsons Dis. 2013;3(2):85-103
pubmed: 23938341
Lancet Neurol. 2014 Oct;13(10):1045-60
pubmed: 25231526
Nat Commun. 2019 Mar 7;10(1):973
pubmed: 30846695
Proc Natl Acad Sci U S A. 2013 May 7;110(19):E1817-26
pubmed: 23610405
EMBO Mol Med. 2013 May;5(5):691-706
pubmed: 23606558
Biochem Soc Trans. 2015 Jun;43(3):434-41
pubmed: 26009187
Sci Rep. 2016 Nov 09;6:36669
pubmed: 27827408
Cell Calcium. 2018 Jan;69:112-121
pubmed: 28689729
Biochim Biophys Acta. 2015 May;1853(5):1130-44
pubmed: 25661197
eNeuro. 2016 May 23;3(2):
pubmed: 27257626
Trends Biochem Sci. 2021 Dec;46(12):960-975
pubmed: 34384657
Nat Chem Biol. 2009 Apr;5(4):220-6
pubmed: 19234453
Elife. 2018 Nov 27;7:
pubmed: 30479274