TIMM23 encodes an essential inner mitochondrial membrane core subunit of the TIM23 presequence translocase. Together with TIMM17A/B and TIMM50, it supports import of nuclear-encoded, presequence-containing mitochondrial proteins into the matrix and lateral insertion of selected inner-membrane proteins; it also has a supported non-core role in PINK1-linked stress-induced mitophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0030150 protein import into mitochondrial matrix | IBA GO_REF:0000033 | ACCEPT | Summary: Correct and core. TIMM23-containing TIM23 translocase imports presequence-containing proteins into the mitochondrial matrix. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md Most mitochondrial proteins are nuclear encoded and must be imported into mitochondria. The **TIM23 complex** (also called the **presequence translocase**) is the major inner-membrane translocase for **presequence-containing precursor proteins**, handling a large fraction of mitochondrial protein biogenesis. |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a **core subunit** of the TIM23 inner membrane translocase. |
| GO:0008320 protein transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Accepted as TIMM23 contribution to TIM23-dependent protein translocation across the mitochondrial inner membrane. TIMM23 is essential in the translocase core, even though recent structural work emphasizes Tim17-family subunits as the dominant translocation cavity. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md **TIMM23 is essential** within the TIM23 presequence translocase core, but **Tim17-family proteins** appear to provide the dominant **translocation cavity** driven by conserved electrostatics (negative charges). |
| GO:0005743 mitochondrial inner membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IEA GO_REF:0000002 | ACCEPT | Summary: Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a **core subunit** of the TIM23 inner membrane translocase. |
| GO:0008320 protein transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: Accepted as TIMM23 contribution to TIM23-dependent protein translocation across the mitochondrial inner membrane. TIMM23 is essential in the translocase core, even though recent structural work emphasizes Tim17-family subunits as the dominant translocation cavity. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md **TIMM23 is essential** within the TIM23 presequence translocase core, but **Tim17-family proteins** appear to provide the dominant **translocation cavity** driven by conserved electrostatics (negative charges). |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Correct but too broad; the more specific supported function is protein transmembrane transporter activity in the TIM23 presequence translocase. Reason: Use GO:0008320 protein transmembrane transporter activity and TIM23 complex annotations rather than generic transmembrane transporter activity. |
| GO:0030150 protein import into mitochondrial matrix | IEA GO_REF:0000002 | ACCEPT | Summary: Correct and core. TIMM23-containing TIM23 translocase imports presequence-containing proteins into the mitochondrial matrix. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md Most mitochondrial proteins are nuclear encoded and must be imported into mitochondria. The **TIM23 complex** (also called the **presequence translocase**) is the major inner-membrane translocase for **presequence-containing precursor proteins**, handling a large fraction of mitochondrial protein biogenesis. |
| GO:0005515 protein binding | IPI PMID:23260140 MITRAC links mitochondrial protein translocation to respirat... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:23263864 Methylation-controlled J-protein MCJ acts in the import of p... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0008320 protein transmembrane transporter activity | ISS GO_REF:0000024 | ACCEPT | Summary: Accepted as TIMM23 contribution to TIM23-dependent protein translocation across the mitochondrial inner membrane. TIMM23 is essential in the translocase core, even though recent structural work emphasizes Tim17-family subunits as the dominant translocation cavity. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md **TIMM23 is essential** within the TIM23 presequence translocase core, but **Tim17-family proteins** appear to provide the dominant **translocation cavity** driven by conserved electrostatics (negative charges). |
| GO:0005743 mitochondrial inner membrane | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a **core subunit** of the TIM23 inner membrane translocase. |
| GO:0006886 intracellular protein transport | NAS PMID:10339406 Genetic and structural characterization of the human mitocho... | MARK AS OVER ANNOTATED | Summary: Correct but broad. TIMM23 is specifically involved in mitochondrial protein import via the TIM23 presequence translocase. Reason: The specific mitochondrial matrix import and TIM23 translocase terms capture the supported biology better than generic intracellular protein transport. |
| GO:0030150 protein import into mitochondrial matrix | TAS PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct and core. TIMM23-containing TIM23 translocase imports presequence-containing proteins into the mitochondrial matrix. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md Most mitochondrial proteins are nuclear encoded and must be imported into mitochondria. The **TIM23 complex** (also called the **presequence translocase**) is the major inner-membrane translocase for **presequence-containing precursor proteins**, handling a large fraction of mitochondrial protein biogenesis. |
| GO:0005739 mitochondrion | IDA GO_REF:0000052 | MARK AS OVER ANNOTATED | Summary: Correct but broad. TIMM23 is specifically localized to the mitochondrial inner membrane and TIM23 complex. Reason: Prefer mitochondrial inner membrane/TIM23 complex annotations over generic mitochondrion. |
| GO:0005739 mitochondrion | HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an... | MARK AS OVER ANNOTATED | Summary: Correct but broad. TIMM23 is specifically localized to the mitochondrial inner membrane and TIM23 complex. Reason: Prefer mitochondrial inner membrane/TIM23 complex annotations over generic mitochondrion. |
| GO:0005515 protein binding | IPI PMID:37160114 TIM23 facilitates PINK1 activation by safeguarding against O... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0061734 type 2 mitophagy | IMP PMID:37160114 TIM23 facilitates PINK1 activation by safeguarding against O... | KEEP AS NON CORE | Summary: Supported as a non-core stress-response role. TIMM23 can help PINK1 accumulate during depolarization-linked mitophagy, but its primary function is TIM23 presequence translocase protein import. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md Has a role in the activation of stress-induced mitophagy by protecting PINK1 from OMA1-mediated degradation and facilitating its accumulation at the outer mitochondrial membrane in response to depolarization |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IDA PMID:30598479 ROMO1 is a constituent of the human presequence translocase ... | ACCEPT | Summary: Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a **core subunit** of the TIM23 inner membrane translocase. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:25997101 QIL1 is a novel mitochondrial protein required for MICOS com... | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:20053669 Role of Magmas in protein transport and human mitochondria b... | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005743 mitochondrial inner membrane | IDA PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005744 TIM23 mitochondrial import inner membrane translocase complex | IDA PMID:10339406 Genetic and structural characterization of the human mitocho... | ACCEPT | Summary: Correct. TIMM23 is a core component of the TIM23 mitochondrial inner-membrane presequence translocase complex. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a **core subunit** of the TIM23 inner membrane translocase. |
| GO:0005743 mitochondrial inner membrane | TAS PMID:14726512 Organization and function of the small Tim complexes acting ... | ACCEPT | Summary: Correct. TIMM23 is an integral mitochondrial inner membrane component of the TIM23 translocase. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
| GO:0005515 protein binding | IPI PMID:15044455 Tim50, a component of the mitochondrial translocator, regula... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic for TIMM23. The informative annotations are TIM23 complex membership, TIMM50/TIMM17/TIMM21/PINK1-related context, and translocase function. Reason: Documented interactions should be represented by specific complex or pathway annotations rather than generic protein binding. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:15044455 Tim50, a component of the mitochondrial translocator, regula... | ACCEPT | Summary: Supported. TIMM23 has an intermembrane-space-facing region within the inner-membrane TIM23 machinery. Supporting Evidence: file:human/TIMM23/TIMM23-deep-research-falcon.md TIMM23 is a core subunit of the presequence translocase that, together with TOM and other TIM23 subunits, mediates import of presequence-containing proteins into the matrix and inner membrane. |
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Download this section (compressed HTML)Q: Which human TIMM23-containing TIM23 cores differ functionally between TIMM17A and TIMM17B paralog contexts?
Q: How separable is TIMM23 structural support of the presequence translocase from its PINK1-linked mitophagy role under depolarizing stress?
Experiment: Use TIMM23 interface mutants in rescue cells and compare TIM23 complex assembly, matrix import substrates, TIM23SORT substrates, and Tim17/TIMM50 interactions by BN-PAGE and in vitro import assays.
Hypothesis: TIMM23 contributes primarily as an essential structural/regulatory core subunit while TIMM17-family proteins form the dominant presequence translocation cavity.
Experiment: Test TIMM23 mutants that preserve TIM23 complex assembly but disrupt PINK1 association, then measure PINK1 stabilization, PRKN recruitment, and matrix/import substrate flux.
Hypothesis: TIMM23-PINK1 interaction during mitochondrial depolarization is a stress-specific function separable from basal TIM23 import.
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