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BID links ferroptosis to mitochondrial cell death pathways
Sandra Neitemeier1, Anja Jelinek1, Vincenzo Laino1
1Institut für Pharmakologie und Klinische Pharmazie, Biochemisch-Pharmakologisches Centrum Marburg, Philipps-Universität Marburg, Karl-von-Frisch-Straße 1, 35032 Marburg, Germany.
Redox Biology
|April 7, 2017
Summary
Ferroptosis, an oxidative cell death pathway, involves mitochondrial damage mediated by BID. Targeting BID offers neuroprotection against ferroptosis and oxytosis, revealing a key link in oxidative cell death.
Area of Science:
- Cellular Biology
- Biochemistry
- Neuroscience
Background:
- Ferroptosis is an oxidative, iron-dependent cell death pathway distinct from apoptosis.
- The role of mitochondrial damage in ferroptosis remains unclear.
- Oxidative cell death paradigms share overlapping features.
Purpose of the Study:
- Investigate the role of mitochondrial damage in ferroptosis.
- Elucidate the biochemical pathways linking ferroptosis and mitochondrial dysfunction.
- Identify potential therapeutic targets for neuroprotection.
Main Methods:
- Erastin-induced ferroptosis in neuronal cells.
- CRISPR/Cas9-mediated Bid knockout.
- Assessment of mitochondrial integrity, membrane potential, ATP levels, and cell death.
- Pharmacological inhibition of BID, ferroptosis, and oxytosis.
Main Results:
- Erastin-induced ferroptosis involved BID transactivation to mitochondria, mitochondrial membrane potential loss, fragmentation, and reduced ATP.
- Bid knockout protected neuronal cells against both ferroptosis and oxytosis.
- BID inhibition blocked erastin-induced ferroptosis.
- Ferroptosis inhibitors prevented mitochondrial dysfunction and cell death in oxytosis.
Conclusions:
- Mitochondrial transactivation of BID links ferroptosis to mitochondrial damage.
- BID acts as a crucial executioner in ferroptosis-induced mitochondrial demise.
- Targeting BID provides a neuroprotective strategy against oxidative cell death pathways.