Link Lysosomal Failure to Ferroptosis in Human Neurons [May 9, 2023]

Here, the scientists reveal an unexpected role for the lysosomal protein prosaposin (PSAP), the knockdown of which caused the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. Intriguingly, PSAP deficiency caused these dramatic phenotypes only in neurons, but not in other cells. Learn how the authors used Dojindo's Ferroptosis-related products, FerroOrange and Liperfluo for detecting Iron levels and lipid peroxidation, in their study. 

Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Click here for the original article: Ruilin Tian, et. al., Nature Neuroscience (2022)

Point of Interest

- The study reveals pathways that govern neuronal response to chronic oxidative stress, a factor in neurodegenerative diseases.

- Suppression of the lysosomal protein prosaposin makes neurons highly susceptible to oxidative stress. 

- This happens through the induction of lipofuscin formation which sequesters iron.

- Iron accumulation contributes to creating reactive oxygen species and lipid peroxidation, triggering ferroptosis, exclusively in neurons.

Related Techniques

Lipid droplets detection

Lipi-Blue / Green / Red / Deep Red

Intracellular / mitochondrial ferrous ion (Fe²⁺) detection

FerroOrange(intracellular), Mito-FerroGreen(mitochondrial)

Lipid peroxidation detection

Liperfluo(intracellular), MitoPeDPP(mitochondrial)

Lipid Peroxidation Assay

Lipid Peroxidation Probe -BDP 581/591 C11-

Cystine Uptake detection

Cystine Uptake Assay Kit

Total ROS detection

Highly sensitive DCFH-DA or Photo-oxidation Resistant DCFH-DA

Mitochondrial superoxide detection

toBright ROS Deep Red - Mitochondrial Superoxide Detection

Related Applications

The simultaneous detection of lysosomal function with  intracellular Fe2+

Recent reports suggest that lysosomal neutralization can result in iron depletion, consequently leading to the disruption of cell viability. To verify this, HeLa cells were labeled with FerroOrange for Fe²⁺ detection, and the lysosomal mass and pH were separately detected with LysoPrime DeepRed and pHLys Green (a product currently under development). Co-staining with FerroOrange and Lysosomal dyes demonstrated that Bafilomycin A1 (Baf. A1), an inhibitor of lysosomal acidification, causes iron depletion consistent with the findings reported in the article. Interestingly, the iron chelator, Deferiprone (DFP), did not impact lysosomal pH, suggesting that lysosomal function plays a key role in managing iron homeostasis.

Reference: Ross A Weber, et. al., Mol Cell (2020)

Products in Use
   - FerroOrange
   - pHLys Green*
   - LysoPrime Deep Red

*pHLys Green is available as the "Lysosomal Acidic pH Detection Kit-Green/Deep Red".