Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death.

ABSTRACT:

Objectives

Opioids including morphine and DAMGO activate mu-opioid receptors (MOR), increase intracellular reactive oxygen species (ROS) levels, and induce cell death. Ferrous iron (Fe²⁺) through Fenton-like chemistry increases ROS levels and endolysosomes are "master regulators of iron metabolism" and contain readily-releasable Fe²⁺ stores. However, mechanisms underlying opioid-induced changes in endolysosome iron homeostasis and downstream-signaling events remain unclear.

Methods

We used SH-SY5Y neuroblastoma cells, flow cytometry, and confocal microscopy to measure Fe²⁺ and ROS levels and cell death.

Results

Morphine and DAMGO de-acidified endolysosomes, decreased endolysosome Fe²⁺ levels, increased cytosol and mitochondr

SUBMITTER: Halcrow PW 

PROVIDER: S-EPMC10070011 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature