Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides
Mitochondria possess a double-membrane envelope which is susceptible to insult by pathogenic intracellular aggregates of amyloid-forming peptides, such as the amyloid-beta (1-42) (Aβ42) peptide and the human islet amyloid polypeptide (hIAPP). The molecular composition of membranes plays a pivotal ro...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Membranes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0375/15/5/148 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850127008702398464 |
|---|---|
| author | Raina Marie Seychell Adam El Saghir Gianluca Farrugia Neville Vassallo |
| author_facet | Raina Marie Seychell Adam El Saghir Gianluca Farrugia Neville Vassallo |
| author_sort | Raina Marie Seychell |
| collection | DOAJ |
| description | Mitochondria possess a double-membrane envelope which is susceptible to insult by pathogenic intracellular aggregates of amyloid-forming peptides, such as the amyloid-beta (1-42) (Aβ42) peptide and the human islet amyloid polypeptide (hIAPP). The molecular composition of membranes plays a pivotal role in regulating peptide aggregation and cytotoxicity. Therefore, we hypothesized that modifying the physicochemical properties of mitochondrial model membranes with a small molecule might act as a countermeasure against the formation of, and damage by, membrane-active amyloid peptides. To investigate this, we inserted the natural ubiquinone Coenzyme Q10 (CoQ10) in model mito-mimetic lipid vesicles, and studied how they interacted with Aβ42 and hIAPP peptide monomers and oligomers. Our results demonstrate that the membrane incorporation of CoQ10 significantly attenuated fibrillization of the peptides, whilst also making the membranes more resilient against peptide-induced permeabilization. Furthermore, these protective effects were linked with the ability of CoQ10 to enhance membrane packing in the inner acyl chain region, which increased the mechanical stability of the vesicle membranes. Based on our collective observations, we propose that mitochondrial resilience against toxic biomolecules implicit in protein misfolding disorders such as Alzheimer’s disease and type-2 diabetes, could potentially be enhanced by increasing CoQ10 levels within mitochondria. |
| format | Article |
| id | doaj-art-e7b2a4b2e6274fafb1bb2cf573ded1a4 |
| institution | OA Journals |
| issn | 2077-0375 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj-art-e7b2a4b2e6274fafb1bb2cf573ded1a42025-08-20T02:33:47ZengMDPI AGMembranes2077-03752025-05-0115514810.3390/membranes15050148Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic PeptidesRaina Marie Seychell0Adam El Saghir1Gianluca Farrugia2Neville Vassallo3Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080 Msida, MaltaMitochondria possess a double-membrane envelope which is susceptible to insult by pathogenic intracellular aggregates of amyloid-forming peptides, such as the amyloid-beta (1-42) (Aβ42) peptide and the human islet amyloid polypeptide (hIAPP). The molecular composition of membranes plays a pivotal role in regulating peptide aggregation and cytotoxicity. Therefore, we hypothesized that modifying the physicochemical properties of mitochondrial model membranes with a small molecule might act as a countermeasure against the formation of, and damage by, membrane-active amyloid peptides. To investigate this, we inserted the natural ubiquinone Coenzyme Q10 (CoQ10) in model mito-mimetic lipid vesicles, and studied how they interacted with Aβ42 and hIAPP peptide monomers and oligomers. Our results demonstrate that the membrane incorporation of CoQ10 significantly attenuated fibrillization of the peptides, whilst also making the membranes more resilient against peptide-induced permeabilization. Furthermore, these protective effects were linked with the ability of CoQ10 to enhance membrane packing in the inner acyl chain region, which increased the mechanical stability of the vesicle membranes. Based on our collective observations, we propose that mitochondrial resilience against toxic biomolecules implicit in protein misfolding disorders such as Alzheimer’s disease and type-2 diabetes, could potentially be enhanced by increasing CoQ10 levels within mitochondria.https://www.mdpi.com/2077-0375/15/5/148mitochondriamembranesamyloid peptidescoenzyme Q10lipid vesiclesaggregation |
| spellingShingle | Raina Marie Seychell Adam El Saghir Gianluca Farrugia Neville Vassallo Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides Membranes mitochondria membranes amyloid peptides coenzyme Q10 lipid vesicles aggregation |
| title | Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides |
| title_full | Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides |
| title_fullStr | Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides |
| title_full_unstemmed | Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides |
| title_short | Coenzyme Q10 Enhances Resilience of Mitochondrial-like Membranes Against Amyloidogenic Peptides |
| title_sort | coenzyme q10 enhances resilience of mitochondrial like membranes against amyloidogenic peptides |
| topic | mitochondria membranes amyloid peptides coenzyme Q10 lipid vesicles aggregation |
| url | https://www.mdpi.com/2077-0375/15/5/148 |
| work_keys_str_mv | AT rainamarieseychell coenzymeq10enhancesresilienceofmitochondriallikemembranesagainstamyloidogenicpeptides AT adamelsaghir coenzymeq10enhancesresilienceofmitochondriallikemembranesagainstamyloidogenicpeptides AT gianlucafarrugia coenzymeq10enhancesresilienceofmitochondriallikemembranesagainstamyloidogenicpeptides AT nevillevassallo coenzymeq10enhancesresilienceofmitochondriallikemembranesagainstamyloidogenicpeptides |