Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein–Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1)
Abstract
:1. Introduction
2. Results
2.1. APOE Accumulates in the MAMs of Human Cultured Hepatocytes, Equally Evident for APOE3 and APOE4
2.2. The Co-Localization of MERC-forming Proteins and Expression of MAM Markers Is Similar in the Presence of APOE3 and APOE4 in Cultured Hepatocytes and the Livers of Mice
2.3. Identification of TOMM40 and Other Mitochondrial and Non-Mitochondrial Proteins as APOE Interaction Partners in Human Cultured Hepatocytes
2.4. LONP1, TOMM40 and VDAC1 Share Cellular Localizations with APOE, Particularly in MAMs, Which Was Equally Evident in APOE3- and APOE4-Transfected Cells
2.5. The UPR and ER Stress Provokes the Accumulation of APOE and LONP1 in MAMs, Strengthening Their Interaction
3. Discussion
4. Materials and Methods
4.1. Cultivation of Human Hepatoma Cells
4.2. APOE3 and APOE4 Plasmid DNA Construction and Transformation and Transient Transfection of Human Hepatoma Cells
4.3. Isolation of Subcellular Fractions
4.4. Co-Immunoprecipitation (co-IP)
4.5. Proteome Analysis
4.6. APOE-Targeted Replacement Mice
4.7. Western Blotting
4.8. Proximity Ligation Assay (PLA)
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein | Antibody | Company | |
---|---|---|---|
APOE | Apolipoprotein E | sc-13521 | Santa Cruz, Dallas, TX, USA |
CANX | Calnexin | ab13504 | Abcam, Cambridge, UK |
COX | Cytochrome C oxidase | ab110413 | Abcam, Cambridge, UK |
GRP75 | Glucose-regulated protein 75 | ORB214063 | Biorbyt, Cambridge, UK |
FIS1 | Mitochondrial fission 1 protein | 10956-1-AP | Proteintech, Planegg-Martinsried, Germany |
LONP1 | Lon protease | 15440-1-AP | Proteintech, Planegg-Martinsried, Germany |
MFN2 | Mitofusin 2 | 12186-1-AP | Proteintech, Planegg-Martinsried, Germany |
PEMT | Phosphatidylethanolamine N-methyltransferase | ORB46023 | Biorbyt, Cambridge, UK |
SIGMAR1 | Sigma non-opioid intracellular receptor 1 | 15168-1-AP | Proteintech, Planegg-Martinsried, Germany |
TFAM | Mitochondrial transcription factor A | sc-166965 | Santa Cruz, Dallas, TX, USA |
TOMM40 | Translocase of outer mitochondria membrane 40 | 18409-1-AP | Proteintech, Planegg-Martinsried, Germany |
TUB | Tubulin | ab7291 | Abcam, Cambridge, UK |
VDAC1 | Voltage-dependent anion-selective channel 1 | sc-8828 | Santa Cruz, Dallas, TX, USA |
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Rueter, J.; Rimbach, G.; Bilke, S.; Tholey, A.; Huebbe, P. Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein–Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1). Int. J. Mol. Sci. 2024, 25, 10597. https://doi.org/10.3390/ijms251910597
Rueter J, Rimbach G, Bilke S, Tholey A, Huebbe P. Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein–Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1). International Journal of Molecular Sciences. 2024; 25(19):10597. https://doi.org/10.3390/ijms251910597
Chicago/Turabian StyleRueter, Johanna, Gerald Rimbach, Stephanie Bilke, Andreas Tholey, and Patricia Huebbe. 2024. "Readdressing the Localization of Apolipoprotein E (APOE) in Mitochondria-Associated Endoplasmic Reticulum (ER) Membranes (MAMs): An Investigation of the Hepatic Protein–Protein Interactions of APOE with the Mitochondrial Proteins Lon Protease (LONP1), Mitochondrial Import Receptor Subunit TOM40 (TOMM40) and Voltage-Dependent Anion-Selective Channel 1 (VDAC1)" International Journal of Molecular Sciences 25, no. 19: 10597. https://doi.org/10.3390/ijms251910597