FSP1 Protein - Ferroptosis Suppressor Protein 1

FSP1 Protein - Ferroptosis Suppressor Protein 1

Introduction

Fsp1 Protein Ferroptosis Suppressor Protein 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

FSP1 Protein - Ferroptosis Suppressor Protein 1

Introduction

Fsp1 Protein Ferroptosis Suppressor Protein 1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein"> [@nadhdependent]
<table> [@fspa]
<tr><th colspan="2" style="background:#f0f0f0;">FSP1 Protein (Ferroptosis Suppressor Protein 1)</th></tr> [@coenzyme]
<tr><td><b>Protein Name</b></td><td>Ferroptosis Suppressor Protein 1 (FSP1)</td></tr> [^5]
<tr><td><b>Gene</b></td><td>[FSP1 (AIFM2)](/genes/fsp1)</td></tr>
<tr><td><b>UniProt ID</b></td><td>[Q9NSW9](https://www.uniprot.org/uniprot/Q9NSW9)</td></tr>
<tr><td><b>Alternative Names</b></td><td>AIFM2, Apoptosis-Inducing Factor Mitochondrial 2</td></tr>
<tr><td><b>Molecular Weight</b></td><td>~35 kDa</td></tr>
<tr><td><b>Subcellular Localization</b></td><td>Mitochondria, plasma membrane, peroxisomes</td></tr>
<tr><td><b>Protein Family</b></td><td>AIF family, NADH:quinone oxidoreductases</td></tr>
<tr><td><b>Structure</b></td><td>FAD/NADH binding domains</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/chronic-kidney-disease" style="color:#ef9a9a">Chronic Kidney Disease</a>, <a href="/wiki/fibrosis" style="color:#ef9a9a">Fibrosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">129 edges</a></td>
</tr>
</table>
</div>

Overview

FSP1 ([Ferroptosis](/entities/ferroptosis) Suppressor Protein 1) is a NADH-dependent coenzyme Q reductase that suppresses ferroptosis through a GPX4-independent mechanism. Originally named AIFM2 ([Apoptosis](/entities/apoptosis) Factor Mitochondrial 2), it was renamed FSP1 due to its primary role in ferroptosis suppression. The protein catalyzes the reduction of CoQ10 to ubiquinol, which acts as a potent lipophilic antioxidant in membranes.

Protein Structure

Domain Architecture

FSP1 contains key structural features:

• N-terminal mitochondrial targeting: Signal sequence for mitochondrial import
• FAD binding domain: Flavin adenine dinucleotide cofactor
• NADH binding site: Electron donor for CoQ reduction
• C-terminal transmembrane anchor: Membrane association

Catalytic Mechanism

The enzyme operates through a ping-pong mechanism:

Normal Function

Coenzyme Q Reduction

FSP1 catalyzes:

• NADH-dependent: Uses NADH as electron donor
• CoQ10 reduction: Converts ubiquinone to ubiquinol
• Membrane localization: Works in mitochondrial and plasma membranes

Antioxidant Activity

Ubiquinol (CoQ10H2) generated by FSP1:

• Lipophilic antioxidant: Neutralizes lipid peroxyl radicals
• Chain termination: Prevents propagation of lipid peroxidation
• Membrane protection: Protects against oxidative damage

Role in Neurodegeneration

Ferroptosis in Neurons

FSP1 provides GPX4-independent ferroptosis protection:

• Alternative pathway: Important when GPX4 is compromised
• Neuronal protection: May protect against ferroptotic death
• Age-related decline: Expression may decrease with age

Potential Therapeutic Applications

• Neuroprotection: FSP1 activators may protect [neurons](/entities/neurons)
• CoQ10 connection: Links to CoQ10 deficiency in PD
• Combination therapy: With GPX4 modulators

Therapeutic Targeting

FSP1 Inhibitors (Cancer Therapy)

| Compound | Mechanism | Stage | Notes |
|----------|-----------|-------|-------|
| iFSP1 | Direct inhibition | Research | First selective FSP1 inhibitor |
| Screening compounds | Various | Discovery | Ongoing efforts |

FSP1 Activators (Neuroprotection)

| Strategy | Approach | Status |
|----------|----------|--------|
| NAD+ precursors | Increase NADH | Research |
| FSP1 expression | Gene therapy | Preclinical |
| CoQ10 supplementation | Substrate availability | Clinical trials |

Protein Interactions

| Partner | Interaction Type | Function |
|---------|-----------------|----------|
| CoQ10 | Substrate | Electron acceptor |
| NADH | Substrate | Electron donor |
| FAD | Cofactor | Electron transfer |
| Mitochondrial complex I | Metabolic link | Electron transport |

Key Publications

Background

The study of Fsp1 Protein Ferroptosis Suppressor Protein 1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• FSP1 Gene
• [GPX4 Protein](/proteins/gpx4-protein)
• [SLC7A11 Protein](/proteins/slc7a11-protein)
• [Ferroptosis Pathway](/mechanisms/ferroptosis-pathway)
• [Mitochondrial Dysfunction Pathway](/mechanisms/mitochondrial-dysfunction)
• [Oxidative Stress Pathway](/mechanisms/oxidative-stress)

External Links

• [UniProt: Q9NSW9](https://www.uniprot.org/uniprot/Q9NSW9)
• [PDB: 6H53 (structure)](https://www.ebi.ac.uk/pdbe/entry/pdb/6h53)
• [AlphaFold Model](https://alphafold.ebi.ac.uk/entry/Q9NSW9)
• [GeneCards: FSP1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=FSP1)

References