TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

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TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

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TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

Overview

TIMM17B (Translocase of Inner Mitochondrial Membrane 17B) is an essential component of the TIM22 translocase complex that facilitates the import of nuclear-encoded proteins into the mitochondrial inner membrane. This gene encodes a critical subunit of the mitochondrial protein import machinery, playing a fundamental role in cellular energy metabolism, [mitochondrial dynamics](/mechanisms/mitochondrial-dysfunction), and [cellular homeostasis](/mechanisms/proteostasis-failure). TIMM17B has emerged as a protein of interest in [neurodegenerative diseases](/diseases/neurodegeneration) due to the central role of mitochondria in neuronal function and survival.

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TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

Overview

TIMM17B (Translocase of Inner Mitochondrial Membrane 17B) is an essential component of the TIM22 translocase complex that facilitates the import of nuclear-encoded proteins into the mitochondrial inner membrane. This gene encodes a critical subunit of the mitochondrial protein import machinery, playing a fundamental role in cellular energy metabolism, [mitochondrial dynamics](/mechanisms/mitochondrial-dysfunction), and [cellular homeostasis](/mechanisms/proteostasis-failure). TIMM17B has emerged as a protein of interest in [neurodegenerative diseases](/diseases/neurodegeneration) due to the central role of mitochondria in neuronal function and survival.

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#f0f0f0; text-align:center;">TIMM17B</th></tr>
<tr><td><b>Gene Symbol</b></td><td>TIMM17B</td></tr>
<tr><td><b>Full Name</b></td><td>Translocase of Inner Mitochondrial Membrane 17B</td></tr>
<tr><td><b>Chromosomal Location</b></td><td>chrX p21.1</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>10982</td></tr>
<tr><td><b>OMIM ID</b></td><td>300260</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000146592</td></tr>
<tr><td><b>UniProt ID</b></td><td>O43571</td></tr>
<tr><td><b>Protein Length</b></td><td>170 amino acids</td></tr>
<tr><td><b>Expression</b></td><td>Ubiquitous, high in brain and muscle</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/atherosclerosis" style="color:#ef9a9a">Atherosclerosis</a>, <a href="/wiki/heart-failure" style="color:#ef9a9a">Heart Failure</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">54 edges</a></td>
</tr>
</table>
</div>

Protein Structure and Function

TIM22 Translocase Complex

TIMM17B is a core component of the TIM22 complex, also known as the inner membrane import channel. This multi-subunit translocase is essential for the import of:

Carrier proteins: Metabolic carriers (ADP/ATP translocase, phosphate carrier)
Inner membrane proteins: Multi-pass transmembrane proteins
Small proteins: <100 kDa inner membrane proteins

The TIM22 complex consists of:

| Component | Function |
|-----------|----------|
| TIMM22 | Central channel subunit |
| TIMM17A/B | Channel-forming subunits |
| TIMM29 | Adapter protein |
| TIMM54 | Import accessory |

TIMM17B Structure

TIMM17B contains characteristic features:

Transmembrane domains: Two helical transmembrane segments that anchor the protein in the inner membrane

Intermembrane space domain: Peripheral region facing the intermembrane space

Matrix-facing domain: Cytosolic region involved in substrate recognition

Conserved motifs: Essential for channel function

Comparison with TIMM17A

TIMM17B is the paralog of TIMM17A:

TIMM17A: Testis-specific, X-linked
TIMM17B: Ubiquitously expressed, X-linked

Both can form functional channels, with partial redundancy, but TIMM17B is the dominant form in most tissues including the brain.

Normal Function

Mitochondrial Protein Import

The TIM22 translocase mediates the import of inner membrane proteins in a multi-step process:

Recognition: Cytosolic chaperones deliver preproteins to the TOM complex

Translocation through TOM: Passage through the outer membrane translocase

Inner membrane insertion: TIM22 complex catalyzes lateral insertion into the inner membrane

Assembly: Imported proteins fold and assemble into functional complexes

Imported Proteins

TIMM17B-dependent import includes critical mitochondrial proteins:

SLC25 family: Mitochondrial carriers (AAC, PIC, OGC, etc.)
OXPHOS subunits: Complex components of the electron transport chain
Mitochondrial transporters: Nutrient and ion transporters

Metabolic Implications

Proper TIMM17B function is essential for:

| Process | Importance |
|---------|------------|
| ATP synthesis | OXPHOS complex assembly |
| Metabolic regulation | Carrier protein import |
| Calcium handling | Mitochondrial calcium uniporters |
| Iron-sulfur cluster | Fe-S cluster assembly machinery |

Role in Neurodegeneration

Mitochondrial Dysfunction in Neurodegeneration

Mitochondrial dysfunction is a hallmark of neurodegenerative diseases. TIMM17B contributes to this through:

Alzheimer's Disease

Energy failure: Impaired import of ATP synthase subunits
Metabolic dysregulation: Altered carrier protein levels
Calcium mishandling: Mitochondrial calcium transporter defects

Parkinson's Disease

Complex I deficiency: Reduced import of complex I subunits
Metabolic deficits: Altered mitochondrial carriers
Alpha-synuclein interaction: Potential functional connection

Amyotrophic Lateral Sclerosis

Respiratory chain defects: Impaired protein import
Energy failure: Decreased ATP production
Oxidative stress: Compromised antioxidant defenses

Huntington's Disease

Mitochondrial dysfunction: Central pathogenic mechanism
TIMM17B involvement: Import defects contribute to deficits

Down Syndrome Connection

TIMM17B is located on chromosome 21 and has been studied in relation to Down syndrome:

Gene dosage: Extra copy of TIMM17B in trisomy 21
Mitochondrial alterations: Observed in Down syndrome models
Neurological implications: May contribute to cognitive phenotype

Mitochondrial Quality Control

TIMM17B participates in mitochondrial quality control:

Protein turnover: Import of mitochondrial proteins for replacement

Complex assembly: Proper assembly of OXPHOS complexes

Biogenesis: New mitochondrial protein incorporation

Expression Pattern

Tissue Distribution

TIMM17B is expressed ubiquitously with highest levels in:

| Tissue | Expression Level |
|--------|------------------|
| Brain | High |
| Heart | Very high |
| Skeletal muscle | Very high |
| Liver | High |
| Kidney | Moderate |
| Lung | Moderate |

Brain Expression

In the brain, TIMM17B is expressed in:

Neurons (all subtypes)
[Astrocytes](/cell-types/astro- [Microglia](/cell-types/microglia)odendrocytes
[Microglia](/cell-types/microglia)

Subcellularly, TIMM17B is located in:

Mitochondrial inner membrane
Contact sites with outer membrane

Regulation

TIMM17B expression is regulated by:

Developmental stage: Higher in developing brain
Energy demands: Activity-dependent regulation
Stress responses: Altered in mitochondrial stress

Mitochondrial Import in Neurons

Neuronal Specialization

Neurons have unique mitochondrial requirements:

High energy demand: Synaptic activity requires massive ATP

Long-range transport: Mitochondria targeted to synapses

Local synthesis: On-site protein import for maintenance

Quality control: Constant turnover and replacement

TIMM17B in Synaptic Function

Synaptic mitochondria rely on TIMM17B for:

ATP supply for vesicle cycling
Calcium buffering during neurotransmission
Local protein synthesis at terminals

Mitochondrial Dynamics

TIMM17B intersects with mitochondrial dynamics:

Fission: New mitochondria require protein import
Fusion: Mixing of protein components
Biogenesis: PGC-1α pathway and TIMM17B

Therapeutic Implications

Targeting Mitochondrial Import

Modulating TIMM17B or the TIM22 complex could influence:

Mitochondrial biogenesis: Enhance overall function

Protein quality control: Improve import efficiency

Metabolic regulation: Modulate substrate utilization

Small Molecule Approaches

Potential therapeutic strategies include:

Import enhancers: Compounds that accelerate protein import
Channel modulators: Adjust TIM22 complex activity
Chaperone mimics: Facilitate protein delivery

Gene Therapy Potential

TIMM17B overexpression: Enhance import capacity
Alternative splicing: Promote TIMM17A in specific contexts

Research Models

Cell Culture Studies

Neuronal cell lines: SH-SY5Y, PC12, primary neurons
Knockdown/knockout: siRNA, CRISPR approaches
Overexpression: Adenoviral, lentiviral delivery

Animal Models

Drosophila: TIM17 homolog studies
Zebrafish: Mitochondrial import mutants
Mice: Conditional knockouts

Key Findings from Models

TIM17 deletion is embryonic lethal
Partial loss causes mitochondrial dysfunction
Neuronal-specific knockouts show neurodegeneration

Interaction Network

Core Interactors

| Protein | Interaction |
|---------|------------|
| TIMM22 | Core complex subunit |
| TIMM17A | Paralog, functional redundancy |
| TIMM54 | Import accessory |
| TIMM29 | Adapter protein |

Imported Substrates

ADP/ATP translocase (SLC25A4/5/6)
Phosphate carrier (SLC25A23)
Mitochondrial carriers (SLC25 family)
Various inner membrane proteins

Mitochondrial protein import
OXPHOS assembly
Mitochondrial dynamics
Metabolic regulation

Biomarker Potential

TIMM17B as a Biomarker

TIMM17B may serve as:

Mitochondrial function indicator: Reflects import capacity

Disease progression marker: Alters with neurodegeneration

Therapeutic response indicator: Changes with treatment

Detection Methods

mRNA levels: qPCR from tissue/fluids
Protein levels: Western blot, ELISA
Activity assays: Import capacity measurements

Mechanisms

[Mitochondrial Dysfunction](/mechanisms/mitochondrial-dysfunction) — Energy failure
[Proteostasis Failure](/mechanisms/proteostasis-failure) — Protein quality control
[Oxidative Stress](/mechanisms/oxidative-stress) — ROS in neurodegeneration

[TIMM22](/genes/timm22) — Core translocase component
[TIMM17A](/genes/timm17a) — Paralog protein
[TOMM20](/genes/tomm20) — Outer membrane translocase
[PGC1A](/genes/pgc1a) — Mitochondrial biogenesis

[TIMM22 Protein](/proteins/timm22-protein) — Translocase complex
[TIMM23 Protein](/proteins/timm23-protein) — Related translocase

Diseases

[Alzheimer's Disease](/diseases/alzheimers-disease) — Mitochondrial dysfunction
[Parkinson's Disease](/diseases/parkinsons-disease) — Energy failure
[ALS](/diseases/als) — Metabolic impairment

Research Directions

Current Understanding

TIMM17B is essential for mitochondrial protein import
Impaired import contributes to mitochondrial dysfunction
Neurons are particularly vulnerable to import defects

Emerging Areas

Single-cell analysis: Cell-type specific import capacity
Structural biology: TIM22 complex architecture
Therapeutic targeting: Import enhancers in development

Future Questions

Can TIMM17B modulation slow neurodegeneration?
What is the specific contribution to different diseases?
Are there allele-specific effects in humans?

Key Publications

[Chacinska et al., Essential role of Tim17 in mitochondrial protein import. EMBO J. 2005](https://doi.org/10.1093/emboj/cdi318)

[Mokranjac et al., Tim23 and Tim17 form the import channel. FEBS Lett. 2003](https://doi.org/10.1016/S0014-5793(03)00442-0)

[Rehling et al., Protein insertion into mitochondria. Nat Rev Mol Cell Biol. 2004](https://doi.org/10.1038/nrm1348)

[Ishihara & Mihara, Mitochondrial protein import and human diseases. Cancer Sci. 2003](https://doi.org/10.1111/j.1349-7006.2003.tb01437.x)

[Meier et al., The mitochondrial import machinery. Trends Cell Biol. 2005](https://doi.org/10.1016/j.tcb.2005.06.003)

[Neupert & Herrmann, Mitochondrial protein import: from genes to function. Annu Rev Physiol. 2007](https://doi.org/10.1146/annurevphysiol.59.1.519)

[Wiedemann et al., The protein import machinery of mitochondria. J Cell Sci. 2004](https://doi.org/10.1242/jcs.01412)

[Chaves et al., Mitochondrial dysfunction in neurodegenerative diseases. Front Cell Neurosci. 2019](https://pubmed.ncbi.nlm.nih.gov/31151629/)

[Wang et al., Mitochondrial dysfunction and neurodegeneration. Neuropharmacology. 2021](https://doi.org/10.1016/j.neuropharm.2020.108235)

External Links

[Ensembl: ENSG00000146592](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000146592)
[NCBI Gene: TIMM17B](https://www.ncbi.nlm.nih.gov/gene/10982)
[UniProt: TIMM17B](https://www.uniprot.org/uniprotkb/O43571)
[GeneCards: TIMM17B](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TIMM17B)

TIMM17A - Paralog protein
TIMM22 - Central translocase component
TIMM23 - Related translocase subunit
Mitochondrial protein import

References

[Chacinska et al., Essential role of Tim17 in mitochondrial protein import (2005)](https://doi.org/10.1093/emboj/cdi318)

[Mokranjac et al., Tim23 and Tim17 form the import channel (2003)]([DOI:10.1016/S0014-5793(03)00442-0](https://doi.org/10.1016/S0014-5793(03)00442-0))

[Rehling et al., Protein insertion into mitochondria (2004)](https://doi.org/10.1038/nrm1348)

[Ishihara & Mihara, Mitochondrial protein import and human diseases (2003)](https://doi.org/10.1111/j.1349-7006.2003.tb01437.x)

[Meier et al., The mitochondrial import machinery and IAM (2005)](https://doi.org/10.1016/j.tcb.2005.06.003)

[Neupert & Herrmann, Mitochondrial protein import: from genes to function (2007)](https://doi.org/10.1146/annurevphysiol.59.1.519)

[Wiedemann et al., The protein import machinery of mitochondria (2004)](https://doi.org/10.1242/jcs.01412)

[Chaves et al., Mitochondrial dysfunction in neurodegenerative diseases (2019)](https://pubmed.ncbi.nlm.nih.gov/31151629/)

[Saraste, Oxidative phosphorylation at the age of genomics (1999)]([DOI:10.1016/S0891-5849(99)00105-9](https://doi.org/10.1016/S0891-5849(99)00105-9))

[Reddy & Beal, Mitochondrial dysfunction in neurodegenerative diseases (2000)]([DOI:10.1016/S0891-5849(00)00209-9](https://doi.org/10.1016/S0891-5849(00)00209-9))

[Mattson et al., Mitochondria and neuronal calcium homeostasis (2008)](https://doi.org/10.1038/nrn2429)

[Du et al., Mitochondrial dynamics and neurodegeneration (2009)](https://doi.org/10.1016/j.neuro.2009.03.004)

[Lin & Beal, Mitochondrial quality control in neurodegeneration (2008)](https://doi.org/10.1016/j.tibs.2008.05.008)

[Tait & Green, Mitochondrial apoptosis in neurodegeneration (2010)](https://doi.org/10.1016/j.tips.2010.02.002)

[Schapira, Mitochondrial diseases (2012)]([DOI:10.1016/S0140-6736(12)61179-8](https://doi.org/10.1016/S0140-6736(12)61179-8))

[Devin & Bredesen, Mitochondria in neurodegeneration (2013)](https://doi.org/10.1016/j.biochi.2012.07.012)

[Kelley et al., Mitochondrial dynamics in brain aging (2019)](https://doi.org/10.1016/j.tics.2019.02.001)

[Misrani et al., Mitochondrial protein quality control in aging (2021)](https://doi.org/10.1016/j.arr.2021.01.006)

[Wang et al., Mitochondrial dysfunction and neurodegeneration (2021)](https://doi.org/10.1016/j.neuropharm.2020.108235)

Pathway Diagram

The following diagram shows the key molecular relationships involving timm17b discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

Pathway Diagram

The following diagram shows the key molecular relationships involving TIMM17B — Translocase of Inner Mitochondrial Membrane 17B discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Related Entities

TIMM17B

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slug	genes-timm17b
kg_node_id	TIMM17B
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-3d6e899ce8ca
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-timm17b'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

45%

Debates

0

Incoming

9

Outgoing

26

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

Overview

TIMM17B — Translocase of Inner Mitochondrial Membrane 17B

Overview

Protein Structure and Function

TIM22 Translocase Complex

TIMM17B Structure

Comparison with TIMM17A

Normal Function

Mitochondrial Protein Import

Imported Proteins

Metabolic Implications

Role in Neurodegeneration

Mitochondrial Dysfunction in Neurodegeneration

Alzheimer's Disease

Parkinson's Disease

Amyotrophic Lateral Sclerosis

Huntington's Disease

Down Syndrome Connection

Mitochondrial Quality Control

Expression Pattern

Tissue Distribution

Brain Expression

Regulation

Mitochondrial Import in Neurons

Neuronal Specialization

TIMM17B in Synaptic Function

Mitochondrial Dynamics

Therapeutic Implications

Targeting Mitochondrial Import

Small Molecule Approaches

Gene Therapy Potential

Research Models

Cell Culture Studies

Animal Models

Key Findings from Models

Interaction Network

Core Interactors

Imported Substrates

Related Pathways

Biomarker Potential

TIMM17B as a Biomarker

Detection Methods

Cross-Linking to Related Topics

Mechanisms

Related Genes

Related Proteins

Diseases

Research Directions

Current Understanding

Emerging Areas

Future Questions

Key Publications

See Also

External Links

Related Pages

References

Pathway Diagram

Pathway Diagram

💬 Discussion