GO:7770015 intermembrane lipid transporter complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:7770015 (intermembrane lipid transporter complex) is a cellular_component term describing a protein complex that moves lipid molecules through an aqueous phase from the outer leaflet of a donor membrane to the outer leaflet of an acceptor membrane.
• Intermembrane lipid transfer is non-vesicular and is essential for maintaining the distinct lipid compositions of organelles such as mitochondria, chloroplasts, and the bacterial outer membrane [1, 3, 4].
• Key protein players include ORP5/8, MIB/MICOS, YdbH/YnbE, and mitochondrial porin, which form or regulate intermembrane bridges and contact sites [2, 3, 4].
• The complex is functionally coupled to mitochondrial protein import, as lipid composition influences TOM/TIM and TOC/TIC translocon assembly and activity [5, 6, 7].
• Dysregulation of intermembrane lipid transport is linked to metabolic stress, neurodegeneration, and cancer cell survival, making it a target for functional genomics [1, 3].
• CRISPR knockout, knock-in, and overexpression models combined with lipidomics and imaging are the primary tools for dissecting this complex in human cells and model organisms [3, 4, 7].
Description
The intermembrane lipid transporter complex (GO:7770015) is a cellular component defined as a protein complex that mediates the transport of lipids between membranes, in which lipid molecules are transferred through an aqueous phase from the outer leaflet of a donor membrane to the outer leaflet of an acceptor membrane. This term captures a fundamental solution to a topological problem: hydrophobic lipids must traverse an aqueous environment to move between organelles that are not connected by vesicular traffic. The complex is therefore central to non-vesicular lipid trafficking at membrane contact sites, including ER-mitochondria and intra-mitochondrial contacts. Researchers study GO:7770015 because lipid asymmetry and organelle-specific lipid composition underpin membrane identity, protein import, and signaling. For example, phosphatidylserine transfer between the ER and mitochondria depends on ORP5/8 and MIB/MICOS complexes that physically link these compartments. In bacteria, the YdbH-YnbE intermembrane bridge maintains lipid homeostasis in the outer membrane, demonstrating that intermembrane lipid transporter complexes are evolutionarily conserved. Understanding this complex also has direct biomedical relevance. Mitochondrial lipid composition influences the assembly and function of the TOM and TIM translocons [5, 7], while chloroplast TOC-TIC supercomplex architecture reveals how lipid environments shape translocon function. Thus, GO:7770015 sits at the intersection of membrane biology, organelle biogenesis, and disease mechanisms.
intermembrane lipid transporter complex At A Glance
| GO ID | GO:7770015 |
|---|---|
| GO term | intermembrane lipid transporter complex |
| Ontology | cellular_component |
| Synonym | lipid transporter complex |
| Major function | Mediates non-vesicular transfer of lipid molecules between membranes through an aqueous phase |
| Directionality | From outer leaflet of donor membrane to outer leaflet of acceptor membrane |
| Substrates | Lipid molecules including phosphatidylserine and other glycerophospholipids |
| Representative components | ORP5/8, MIB/MICOS, YdbH/YnbE, mitochondrial porin |
| Cellular contexts | ER-mitochondria contacts, intra-mitochondrial contacts, bacterial outer membrane, chloroplast translocon regions |
What Is GO:7770015?
GO:7770015, intermembrane lipid transporter complex, is a protein complex that transfers lipid molecules between membranes. The transfer occurs through an aqueous phase, moving lipids from the outer leaflet of a donor membrane to the outer leaflet of an acceptor membrane. This definition distinguishes the term from vesicular transport complexes and from lipid flippases that act within a single membrane. The synonym lipid transporter complex reflects its core biochemical activity.
Why Is intermembrane lipid transporter complex Important in Cell Biology?
GO:7770015 is important because non-vesicular lipid transfer defines the lipid identity of organelles and controls processes ranging from mitochondrial respiration to bacterial envelope integrity. Defects in intermembrane lipid transport alter membrane fluidity, protein import, and stress signaling, which are implicated in metabolic disease, neurodegeneration, and cancer [1, 3, 7]. Because the complex operates at membrane contact sites, it also provides a mechanistic entry point for understanding how organelles communicate independently of vesicle trafficking [3, 4].
• Maintains organelle-specific lipid composition required for mitochondrial and chloroplast function [1, 6].
• Supports non-vesicular phosphatidylserine transport at ER-mitochondria contact sites.
• Regulates bacterial outer membrane lipid homeostasis through intermembrane bridges.
• Coupled to mitochondrial protein import and translocon assembly [5, 7].
• Influences mitochondrial porin oligomerization and membrane organization.
• Provides a target for functional genomics in metabolic and neurodegenerative disease [1, 3].
• Enables experimental dissection of membrane contact site biology using CRISPR models [3, 4].
• Links lipid trafficking to cellular stress responses and organelle quality control.
• Offers a conserved paradigm from bacteria to humans for intermembrane lipid transfer.
• Supports development of lipidomic and imaging assays for organelle crosstalk [3, 8].
What Happens During intermembrane lipid transporter complex?
Donor membrane lipid extraction
In simple terms: The complex first grabs a lipid molecule from the outer surface of the donor membrane.
Intermembrane lipid transfer begins when the transporter complex binds a lipid molecule at the outer leaflet of the donor membrane. This step is non-vesicular and requires a hydrophobic pocket or bridge that shields the lipid from the aqueous cytosol. At ER-mitochondria contacts, ORP5/8 and MIB/MICOS components cooperate to extract phosphatidylserine from the ER membrane for transfer to mitochondria.
Aqueous phase transit
In simple terms: The lipid is carried through the water-filled space between membranes without touching it directly.
The defining feature of GO:7770015 is transit through an aqueous phase. The complex forms a shielded channel or bridge that allows the lipid to move from the donor to the acceptor membrane while avoiding aggregation or mislocalization. In Escherichia coli, YdbH and YnbE form an intermembrane bridge that maintains lipid homeostasis in the outer membrane, illustrating this transit mechanism in a bacterial system.
Acceptor membrane insertion
In simple terms: The lipid is delivered into the outer surface of the target membrane.
After transit, the lipid is inserted into the outer leaflet of the acceptor membrane. This delivery step is coupled to membrane contact site architecture, as seen for intra-mitochondrial contacts that receive phosphatidylserine from the ER. Proper insertion maintains lipid asymmetry and supports downstream processes such as mitochondrial protein import.
Coupling to protein import and translocon function
In simple terms: Lipid delivery helps the protein import machines in mitochondria and chloroplasts work properly.
Intermembrane lipid transport is functionally linked to protein import. The mitochondrial import gate and TOM/TIM translocons require specific lipid environments for assembly and activity [5, 7]. Similarly, the chloroplast TOC-TIC translocon supercomplex operates within a lipid milieu that is shaped by intermembrane lipid transfer. This coupling ensures that organelle biogenesis is coordinated with membrane lipid supply.
Regulation by contact site proteins
In simple terms: Other proteins at membrane contact sites tell the transporter complex when and where to work.
The activity of intermembrane lipid transporter complexes is regulated by contact site proteins that tether membranes and organize the transfer machinery. ORP5/8 and MIB/MICOS link ER-mitochondria and intra-mitochondrial contacts for non-vesicular phosphatidylserine transport. Mitochondrial porin oligomerization also contributes to membrane organization and may influence lipid transfer efficiency.
Key Genes Involved in GO:7770015 intermembrane lipid transporter complex
The following genes and proteins are experimentally implicated in intermembrane lipid transporter complex function, membrane contact site organization, or coupled lipid transfer processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ORP5 | Phosphatidylserine transfer at ER-mitochondria contacts | Knockout alters mitochondrial lipid composition |
| ORP8 | Phosphatidylserine transfer at ER-mitochondria contacts | Knockout alters mitochondrial lipid composition |
| MIB1 | MIB/MICOS component linking ER-mitochondria contacts | Required for non-vesicular phosphatidylserine transport |
| MICOS | Mitochondrial contact site and cristae organizing system | Links intra-mitochondrial contacts to lipid transfer |
| YdbH | Intermembrane bridge in E. coli outer membrane lipid homeostasis | Bacterial model for intermembrane lipid transfer |
| YnbE | Intermembrane bridge partner of YdbH | Bacterial model for intermembrane lipid transfer |
| VDAC1 | Mitochondrial porin with oligomer-based functions | Oligomerization affects membrane organization |
| VDAC2 | Mitochondrial porin family member | Contributes to mitochondrial membrane dynamics |
| VDAC3 | Mitochondrial porin family member | Contributes to mitochondrial membrane dynamics |
| TOMM20 | Mitochondrial import receptor subunit | Lipid environment affects import gate function [5, 7] |
| TOMM40 | Mitochondrial import channel subunit | Lipid environment affects import gate function [5, 7] |
| TIMM23 | Mitochondrial inner membrane translocon subunit | Coupled to lipid-dependent import [5, 7] |
| TOC159 | Chloroplast outer envelope translocon component | TOC-TIC supercomplex architecture |
| TIC20 | Chloroplast inner envelope translocon component | TOC-TIC supercomplex architecture |
| TIC214 | Chloroplast inner envelope translocon component | TOC-TIC supercomplex architecture |
| PRELID1 | Mitochondrial intermembrane space protein | Potential link to lipid transfer and import |
| CHCHD2 | Mitochondrial cristae and contact site protein | Candidate for lipid-import coupling |
| ATAD3A | Mitochondrial inner membrane contact site protein | Candidate for lipid-import coupling |
How Is intermembrane lipid transporter complex Regulated?
Intermembrane lipid transporter complex activity is regulated at the level of membrane contact site assembly and by the lipid composition of the donor and acceptor membranes. ORP5/8 and MIB/MICOS proteins organize ER-mitochondria and intra-mitochondrial contacts that position the transfer machinery for phosphatidylserine transport. Mitochondrial porin oligomerization influences membrane organization and may modulate the efficiency of lipid transfer. In bacteria, YdbH and YnbE form an intermembrane bridge whose integrity is required for outer membrane lipid homeostasis. The complex is also functionally coupled to mitochondrial protein import, so changes in translocon assembly or import activity can feed back on lipid transfer requirements [5, 7].
intermembrane lipid transporter complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ORP5 | Mitochondrial lipid imbalance and metabolic stress | CRISPR knockout in human cell lines |
| ORP8 | ER-mitochondria contact dysfunction | CRISPR knockout and lipidomics |
| MIB1 | Non-vesicular phosphatidylserine transport defects | Knockout and rescue with tagged knock-in |
| YdbH | Bacterial outer membrane lipid homeostasis | E. coli knockout and point mutation |
| VDAC1 | Mitochondrial membrane organization and stress | Oligomerization mutants and overexpression |
Mitochondrial dysfunction and metabolic stress
Altered mitochondrial lipid composition impairs respiratory chain function and organelle quality control, contributing to metabolic stress and mitochondrial disease phenotypes [1, 7]. Because GO:7770015 complexes deliver lipids such as phosphatidylserine to mitochondria, their dysfunction can disrupt cristae architecture and energy metabolism.
Neurodegeneration
Neurons are highly dependent on mitochondrial lipid homeostasis and membrane contact site function. Defects in non-vesicular lipid transfer at ER-mitochondria contacts have been linked to neurodegeneration through impaired mitochondrial dynamics and lipid signaling [1, 3].
Cancer cell survival
Cancer cells reprogram lipid metabolism to support rapid proliferation and stress resistance. Intermembrane lipid transporter complexes that maintain mitochondrial membrane composition may support cancer cell survival under metabolic stress, making them candidate targets for functional genomics [1, 3].
Bacterial envelope integrity and antibiotic susceptibility
In Gram-negative bacteria, intermembrane bridges such as YdbH-YnbE maintain outer membrane lipid homeostasis. Disruption of this system compromises envelope integrity and may alter susceptibility to antibiotics.
From intermembrane lipid transporter complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of ORP5/8 impair phosphatidylserine transfer to mitochondria? | CRISPR knockout in human cells with lipidomics |
| Is the YdbH-YnbE bridge required for outer membrane lipid homeostasis? | E. coli knockout and point mutation |
| How does mitochondrial porin oligomerization affect membrane organization? | Point mutation and tagged knock-in |
| Does MIB/MICOS complex disruption alter ER-mitochondria contacts? | Knockout and contact site imaging |
| Can overexpression of lipid transfer proteins rescue import defects? | Overexpression in mitochondrial reporter cells |
| How does TOC-TIC supercomplex assembly depend on lipid environment? | Chloroplast knockout and proteomics |
How to Study the intermembrane lipid transporter complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Lipidomics | Lipid species abundance and distribution | Quantify phosphatidylserine transfer defects |
| Live-cell fluorescence imaging | Membrane contact site dynamics | Visualize ER-mitochondria contacts |
| Affinity proteomics | Protein-protein interactions | Identify translocon and contact site components [5, 6] |
| Mitochondrial import assay | Protein import efficiency | Test lipid-dependent import [7, 8] |
| CRISPR knockout screening | Gene requirement for lipid homeostasis | Discover new intermembrane transporter components [3, 4] |
| Bacterial genetics | Outer membrane lipid homeostasis | Study YdbH-YnbE bridge function |
| Structural biology | Complex architecture | Determine import gate and translocon structures [5, 6] |
| Oligomerization assays | Porin complex formation | Assess membrane organization |
Lipidomics and mass spectrometry
Lipidomics quantifies the lipid composition of donor and acceptor membranes and detects changes caused by loss or gain of intermembrane lipid transporter complex components. This approach is essential for linking ORP5/8 and MIB/MICOS function to phosphatidylserine distribution.
Fluorescence imaging of membrane contact sites
Live-cell imaging with contact site markers visualizes ER-mitochondria and intra-mitochondrial contacts where intermembrane lipid transfer occurs. Imaging can be combined with knockout or knock-in models to test how specific proteins organize these sites.
Proteomics of translocon and contact site complexes
Affinity purification and mass spectrometry identify protein-protein interactions within mitochondrial and chloroplast translocon complexes, revealing how lipid transfer is coupled to protein import machinery [5, 6].
Functional import assays
In vitro and in vivo protein import assays measure the efficiency of mitochondrial protein import under altered lipid conditions, providing a functional readout for intermembrane lipid transporter complex activity [7, 8].
How CRISPR Can Be Used to Study GO:7770015 intermembrane lipid transporter complex
Knockout
CRISPR knockout of ORP5, ORP8, or MIB/MICOS components in human cell lines disrupts non-vesicular phosphatidylserine transport and alters mitochondrial lipid composition, providing causal evidence for GO:7770015 function. Knockout of YdbH or YnbE in E. coli similarly compromises outer membrane lipid homeostasis.
Point Mutation
Point mutations can dissect the lipid-binding or bridge-forming residues of intermembrane lipid transporter complex proteins. For example, mutating key residues in YdbH or YnbE tests which domains are required for the intermembrane bridge in bacteria. Point mutations in mitochondrial porin can probe oligomerization-dependent membrane organization.
Knock-in
Tagged knock-in of ORP5, ORP8, or MIB1 enables live-cell imaging and affinity purification of the intermembrane lipid transporter complex without overexpression artifacts. Knock-in reporters can also track contact site dynamics under metabolic stress.
Overexpression
Overexpression of lipid transfer proteins can rescue import or lipid homeostasis defects and test sufficiency of individual components. Overexpression models are useful for probing whether increased lipid transfer capacity alters mitochondrial function or stress resistance.
How EDITGENE Supports intermembrane lipid transporter complex Research
Researchers studying intermembrane lipid transporter complex-related genes often need to determine whether a candidate gene is causally involved in lipid transfer, membrane contact site organization, or coupled protein import. Establishing causality requires precise genetic models that isolate loss-of-function, gain-of-function, and localization effects without confounding artifacts.
Contact EDITGENE today to design your custom CRISPR model for intermembrane lipid transporter complex research.
Frequently Asked Questions About intermembrane lipid transporter complex
What is GO:7770015?
GO:7770015 is the Gene Ontology cellular_component term for intermembrane lipid transporter complex, a protein complex that transfers lipid molecules through an aqueous phase from the outer leaflet of a donor membrane to the outer leaflet of an acceptor membrane.
What does the intermembrane lipid transporter complex do?
It mediates non-vesicular lipid transfer between membranes, maintaining organelle-specific lipid composition and supporting processes such as mitochondrial protein import [1, 3, 7].
What genes are involved in the intermembrane lipid transporter complex?
Key genes include ORP5, ORP8, MIB1, MICOS components, YdbH, YnbE, and mitochondrial porins such as VDAC1 [2, 3, 4].
Where does intermembrane lipid transfer occur?
It occurs at membrane contact sites, including ER-mitochondria contacts, intra-mitochondrial contacts, bacterial outer membrane bridges, and chloroplast translocon regions [3, 4, 6].
Why is non-vesicular lipid transfer important?
Non-vesicular transfer allows lipids to move between organelles that are not connected by vesicular traffic, which is essential for membrane identity and organelle function [1, 3].
How is the intermembrane lipid transporter complex linked to disease?
Defects in intermembrane lipid transfer are linked to mitochondrial dysfunction, neurodegeneration, cancer cell survival, and bacterial envelope integrity [1, 3, 4].
What methods are used to study GO:7770015?
Common methods include lipidomics, live-cell imaging of contact sites, affinity proteomics, mitochondrial import assays, and CRISPR screening [3, 5, 7, 8].
Can CRISPR knockout help study intermembrane lipid transport?
Yes, CRISPR knockout of ORP5, ORP8, or MIB/MICOS components disrupts phosphatidylserine transport and alters mitochondrial lipid composition.
What is the role of mitochondrial porin in this complex?
Mitochondrial porin oligomerization contributes to membrane organization and may influence lipid transfer efficiency at mitochondrial membranes.
How does the bacterial YdbH-YnbE bridge relate to GO:7770015?
YdbH and YnbE form an intermembrane bridge that maintains lipid homeostasis in the E. coli outer membrane, providing a conserved bacterial example of intermembrane lipid transfer.
Conclusion
GO:7770015, intermembrane lipid transporter complex, defines a conserved mechanism for non-vesicular lipid transfer between membranes through an aqueous phase. Its components, including ORP5/8, MIB/MICOS, YdbH/YnbE, and mitochondrial porins, are central to organelle lipid homeostasis and coupled protein import [2, 3, 4, 7]. Dysregulation of this complex is linked to mitochondrial dysfunction, neurodegeneration, cancer, and bacterial envelope defects [1, 3, 4]. CRISPR-based knockout, point mutation, knock-in, and overexpression models combined with lipidomics, imaging, and proteomics provide a rigorous path to dissect this complex. EDITGENE offers end-to-end services to build these models and analyze the resulting data for publication-ready mechanistic insights.
References
- 1. Horvath SE et al.. 2013. Lipids of mitochondria.. Prog Lipid Res 52(4):590-614 PMID: 24007978
- 2. Takeda H et al.. 2025. Oligomer-based functions of mitochondrial porin.. Nat Commun 16(1):6854 PMID: 40715117
- 3. Monteiro-Cardoso VF et al.. 2022. ORP5/8 and MIB/MICOS link ER-mitochondria and intra-mitochondrial contacts for non-vesicular transport of phosphatidylserine.. Cell Rep 40(12):111364 PMID: 36130504
- 4. Kumar S et al.. 2024. YdbH and YnbE form an intermembrane bridge to maintain lipid homeostasis in the outer membrane of Escherichia coli.. Proc Natl Acad Sci U S A 121(21):e2321512121 PMID: 38748582
- 5. Araiso Y et al.. 2019. Structure of the mitochondrial import gate reveals distinct preprotein paths.. Nature 575(7782):395-401 PMID: 31600774
- 6. Liu H et al.. 2023. Architecture of chloroplast TOC-TIC translocon supercomplex.. Nature 615(7951):349-357 PMID: 36702157
- 7. Hoffmann JJ et al.. 2022. Crosstalk between Mitochondrial Protein Import and Lipids.. Int J Mol Sci 23(9) PMID: 35563660
- 8. Priesnitz C et al.. 2020. Studying protein import into mitochondria.. Methods Cell Biol 155:45-79 PMID: 32183973
