Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A.

ABSTRACT: Various neurodegenerative disorders are associated with increased brain iron content. Iron is known to cause oxidative stress, which concomitantly promotes cell death. Whereas endolysosomes are known to serve as intracellular iron storage organelles, the consequences of increased iron on endolysosomal functioning, and effects on cell viability upon modulation of endolysosomal iron release remain largely unknown. Here, we show that increasing intracellular iron causes endolysosomal alterations associated with impaired autophagic clearance of intracellular protein aggregates, increased cytosolic oxidative stress and increased cell death. These effects are subject to regulation by NAADP, a potent second messenger reported to target endolysosomal TPCNs (2-pore channels). Consistent with endoly

SUBMITTER: Fernandez B 

PROVIDER: S-EPMC5082776 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature