The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency
Living systems require energy to maintain their existence and perform tasks such as cell division. This energy is stored in several molecular forms in nature, specifically lipids, carbohydrates, and amino acids. At a cellular level, energy is extracted from these complex molecules and transferred to...
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MDPI AG
2025-03-01
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| author | Shashwat Sharma Matthew McKenzie |
| author_facet | Shashwat Sharma Matthew McKenzie |
| author_sort | Shashwat Sharma |
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| description | Living systems require energy to maintain their existence and perform tasks such as cell division. This energy is stored in several molecular forms in nature, specifically lipids, carbohydrates, and amino acids. At a cellular level, energy is extracted from these complex molecules and transferred to adenosine triphosphate (ATP) in the cytoplasm and mitochondria. Within the mitochondria, fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are crucial metabolic processes involved in generating ATP, with defects in these pathways causing mitochondrial disease. Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid β-oxidation disorder (FAOD) affecting 1 to 2 individuals per 100,000. Similar to other mitochondrial disorders, there is no cure for VLCADD, with symptomatic treatment comprising dietary management and supplementation with medium-chain fatty acids to bypass the enzyme deficiency. While this addresses the primary defect in VLCADD, there is growing evidence that other aspects of mitochondrial function are also affected in VLCADD, including secondary defects in OXPHOS function. Here, we review our current understanding of VLCADD with a focus on the associated biochemical and molecular defects that can disrupt multiple aspects of mitochondrial function. We describe the interactions between FAO proteins and the OXPHOS complexes and how these interactions are critical for maintaining the activity of both metabolic pathways. In particular, we describe what is now known about the protein–protein interactions between VLCAD and the OXPHOS supercomplex and how their disruption contributes to overall VLCADD pathogenesis. |
| format | Article |
| id | doaj-art-b413d08b8eaf4708ad065d532b1090e2 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-03-01 |
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| series | Biomolecules |
| spelling | doaj-art-b413d08b8eaf4708ad065d532b1090e22025-08-20T03:43:02ZengMDPI AGBiomolecules2218-273X2025-03-0115341610.3390/biom15030416The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase DeficiencyShashwat Sharma0Matthew McKenzie1School of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 75 Pigdons Road, Waurn Ponds, VIC 3216, AustraliaSchool of Life and Environmental Sciences, Faculty of Science, Engineering and Built Environment, Deakin University, 75 Pigdons Road, Waurn Ponds, VIC 3216, AustraliaLiving systems require energy to maintain their existence and perform tasks such as cell division. This energy is stored in several molecular forms in nature, specifically lipids, carbohydrates, and amino acids. At a cellular level, energy is extracted from these complex molecules and transferred to adenosine triphosphate (ATP) in the cytoplasm and mitochondria. Within the mitochondria, fatty acid β-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are crucial metabolic processes involved in generating ATP, with defects in these pathways causing mitochondrial disease. Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid β-oxidation disorder (FAOD) affecting 1 to 2 individuals per 100,000. Similar to other mitochondrial disorders, there is no cure for VLCADD, with symptomatic treatment comprising dietary management and supplementation with medium-chain fatty acids to bypass the enzyme deficiency. While this addresses the primary defect in VLCADD, there is growing evidence that other aspects of mitochondrial function are also affected in VLCADD, including secondary defects in OXPHOS function. Here, we review our current understanding of VLCADD with a focus on the associated biochemical and molecular defects that can disrupt multiple aspects of mitochondrial function. We describe the interactions between FAO proteins and the OXPHOS complexes and how these interactions are critical for maintaining the activity of both metabolic pathways. In particular, we describe what is now known about the protein–protein interactions between VLCAD and the OXPHOS supercomplex and how their disruption contributes to overall VLCADD pathogenesis.https://www.mdpi.com/2218-273X/15/3/416VLCADDvery long-chain acyl-CoA dehydrogenase deficiencyVLCADvery long-chain acyl-CoA dehydrogenaseFAOfatty acid β-oxidation |
| spellingShingle | Shashwat Sharma Matthew McKenzie The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency Biomolecules VLCADD very long-chain acyl-CoA dehydrogenase deficiency VLCAD very long-chain acyl-CoA dehydrogenase FAO fatty acid β-oxidation |
| title | The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| title_full | The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| title_fullStr | The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| title_full_unstemmed | The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| title_short | The Pathogenesis of Very Long-Chain Acyl-CoA Dehydrogenase Deficiency |
| title_sort | pathogenesis of very long chain acyl coa dehydrogenase deficiency |
| topic | VLCADD very long-chain acyl-CoA dehydrogenase deficiency VLCAD very long-chain acyl-CoA dehydrogenase FAO fatty acid β-oxidation |
| url | https://www.mdpi.com/2218-273X/15/3/416 |
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