DNM1L Gene

DNM1L Gene

Pathway Diagram

```mermaid
flowchart TD
DNM1L["DNM1L<br/>(Dynamin-1-like protein)"]
ROS["ROS<br/>(Reactive Oxygen Species)"]
MITOCHONDRIA["Mitochondria<br/>(Organelle)"]

OPTN["OPTN<br/>(Optineurin)"]
SQSTM1["SQSTM1/p62<br/>(Autophagy receptor)"]
CALCOCO2["CALCOCO2/NDP52<br/>(Autophagy receptor)"]

BCL2["BCL2<br/>(Anti-apoptotic protein)"]
ATM["ATM<br/>(DNA damage response)"]

FISSION["Mitochondrial<br/>Fission"]
DYSFUNCTION["Mitochondrial<br/>Dysfunction"]
AUTOPHAGY["Selective<br/>Autophagy"]

ALS["ALS<br/>(Amyotrophic Lateral Sclerosis)"]
ALZHEIMER["Alzheimer's<br/>Disease"]
PARKINSON["Parkinson's<br/>Disease"]
MS["Multiple<br/>Sclerosis"]

ROS -->|"activates"| DNM1L
DNM1L -->|"expressed_in"| MITOCHONDRIA
DNM1L -->|"promotes"| FISSION

FISSION -->|"leads_to"| DYSFUNCTION
DYSFUNCTION -->|"contributes_to"| ALS
DYSFUNCTION -->|"contributes_to"| ALZHEIMER
DYSFUNCTION -->|"contributes_to"| PARKINSON
DYSFUNCTION -->|"contributes_to"| MS

OPTN -->|"interacts_with"| DNM1L
SQSTM1 -->|"interacts_with"| DNM1L
CALCOCO2 -->|"interacts_with"| DNM1L

OPTN -->|"mediates"| AUTOPHAGY
SQSTM1 -->|"mediates"| AUTOPHAGY
CALCOCO2 -->|"mediates"| AUTOPHAGY

AUTOPHAGY -->|"removes_damaged"| MITOCHONDRIA

BCL2 -->|"interacts_with"| DNM1L
ATM -->|"regulates"| DNM1L

style DNM1L fill:#006494
style AUTOPHAGY fill:#1b5e20
style OPTN fill:#4a1a6b
style SQSTM1 fill:#4a1a6b
style CALCOCO2 fill:#4a1

DNM1L Gene

Pathway Diagram

Introduction

Dnm1L Gene 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-gene">
<table>
<tr><th colspan="2" style="background:#4a90d9; color:white;">DNM1L - Dynamin 1 Like (DRP1)</th></tr>
<tr><td><strong>Full Name</strong></td><td>Dynamin 1 Like (Dynamin-Related Protein 1)</td></tr>
<tr><td><strong>Chromosomal Location</strong></td><td>12p11.21</td></tr>
<tr><td><strong>NCBI Gene ID</strong></td><td>[1759](https://www.ncbi.nlm.nih.gov/gene/1759)</td></tr>
<tr><td><strong>Ensembl ID</strong></td><td>ENSG00000087470</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[O00429](https://www.uniprot.org/uniprot/O00429)</td></tr>
<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), ALS, Huntington's Disease</td></tr>
</table>
</div>

Overview

The DNM1L gene encodes [Dynamin-Related Protein 1](/proteins/drp1-protein) (DRP1), a large GTPase that mediates mitochondrial fission and peroxisomal division. DRP1 is essential for mitochondrial dynamics and has emerged as a critical player in neurodegeneration, as impaired mitochondrial fission/fusion balance contributes to neuronal death[@knott2008].

Function

DRP1 orchestrates mitochondrial fission:

• Mitochondrial fission: DRP1 assembles around mitochondria and mediates membrane scission
• Peroxisomal division: DRP1 controls peroxisome number and morphology
• Mitochondrial quality control: Fission enables selective mitophagy
• [Apoptosis](/entities/apoptosis) regulation: DRP1 translocates to mitochondria during apoptosis
• Synaptic function: DRP1 regulates mitochondrial distribution in [neurons](/entities/neurons)[@van2013]

Structure

DRP1 contains functional domains:

Expression Pattern

DRP1 is expressed throughout the brain:

• High expression in neurons, particularly in synapses
• Expressed in [astrocytes](/entities/astrocytes) and [microglia](/entities/microglia)

Disease Associations

Alzheimer's Disease

• [Aβ](/proteins/amyloid-beta) induces DRP1 translocation to mitochondria
• Enhanced mitochondrial fission contributes to synaptic loss
• DRP1 inhibitors show benefit in AD models[@wang2009]

Parkinson's Disease

• PINK1/Parkin regulate DRP1 for mitophagy
• Mutations in mitochondrial dynamics genes cause PD

ALS

• Mutant SOD1 impairs mitochondrial dynamics
• DRP1-mediated fission is enhanced in ALS

Huntington's Disease

• Mutant [huntingtin](/proteins/huntingtin-protein) alters DRP1 function
• Excessive mitochondrial fission contributes to neuronal death

Key Publications

See Also

• [DRP1 Protein](/proteins/drp1-protein)
• [Mitochondrial Dynamics Pathway](/mechanisms/mitochondrial-dynamics)
• [Alzheimer's Disease](/diseases/alzheimers-disease)

External Links

• [NCBI Gene: DNM1L](https://www.ncbi.nlm.nih.gov/gene/1759)
• [UniProt: O00429](https://www.uniprot.org/uniprot/O00429)

Background

The study of Dnm1L Gene 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.

Brain Atlas Resources

• Allen Human Brain Atlas: [DNM1L expression search](https://human.brain-map.org/microarray/search/show?search_term=DNM1L)
• Allen Mouse Brain Atlas: [DNM1L search](https://mouse.brain-map.org/search/index.html?query=DNM1L)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Developmental Transcriptome: [DNM1L developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=DNM1L)

Molecular Mechanisms

DNM1L (Dynamin 1-Like Protein), also known as DRP1 (Dynamin-Related Protein 1), is a member of the dynamin family of GTPases essential for mitochondrial fission. DRP1 is a 736-amino acid cytosolic protein that translocates to mitochondria during division:

• Oligomerization: Forms ring-like structures around mitochondria
• GTP hydrolysis: Mediates membrane constriction and scission
• Adaptor proteins: Binds to FIS1, MFF, and MiD49/50 on mitochondrial outer membrane
• Post-translational modifications: Phosphorylation, SUMOylation, and ubiquitination regulate its activity

• Mitochondrial dynamics: Balanced fission and fusion maintains mitochondrial health
• Cell division: Required for proper cytokinesis
• Apoptosis: Fragmentation during programmed cell death

Role in Neurodegeneration

• Alzheimer's disease: Aβ promotes DRP1 translocation and excessive fission
• Parkinson's disease: PINK1/Parkin pathway regulates DRP1; mutations cause fragmentation
• Huntington's disease: Mutant huntingtin increases DRP1 activity and mitochondrial dysfunction
• ALS: DRP1 dysregulation contributes to mitochondrial fragmentation

Therapeutic Implications

• DRP1 inhibitors: Small molecules to block excessive fission
• Modulators of PTMs: Targeting phosphorylation/SUMOylation
• Gene therapy: Reducing or restoring DRP1 function

References

Pathway Diagram

The following diagram shows the key molecular relationships involving DNM1L Gene discovered through SciDEX knowledge graph analysis: