HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS
Abstract Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are key bioenergetics pathways. The machineries for both processes are localized in mitochondria. Secondary OXPHOS defects have been documented in patients with primary FAO deficiencies, and vice versa. However, the underlyin...
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Wiley
2024-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202405147 |
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| author | Chaoying Qin Shasha Gong Ting Liang Zhenbo Zhang Jessie Thomas Janice Deng Yaguang Liu Peiqing Hu Bi Zhu Shujie Song Marisol Fernández Ortiz Yuji Ikeno Exing Wang James Lechleiter Susan T. Weintraub Yidong Bai |
| author_facet | Chaoying Qin Shasha Gong Ting Liang Zhenbo Zhang Jessie Thomas Janice Deng Yaguang Liu Peiqing Hu Bi Zhu Shujie Song Marisol Fernández Ortiz Yuji Ikeno Exing Wang James Lechleiter Susan T. Weintraub Yidong Bai |
| author_sort | Chaoying Qin |
| collection | DOAJ |
| description | Abstract Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are key bioenergetics pathways. The machineries for both processes are localized in mitochondria. Secondary OXPHOS defects have been documented in patients with primary FAO deficiencies, and vice versa. However, the underlying mechanisms remain unclear. Intrigued by the observations that regulation of supercomplexes (SCs) assembly in a mouse OXPHOS deficient cell line and its derivatives is associated with the changes in lipid metabolism, a proteomics analysis is carried out and identified mitochondrial trifunctional protein (MTP) subunit alpha (hydroxyacyl‐CoA dehydrogenase trifunctional multienzyme complex subunit alpha, HADHA) as a potential regulatory factor for SCs assembly. HADHA‐Knockdown cells and mouse embryonic fibroblasts (MEFs) derived from HADHA‐Knockout mice displayed both reduced SCs assembly and defective OXPHOS. Stimulation of OXPHOS induced in cell culture by replacing glucose with galactose and of lipid metabolism in mice with a high‐fat diet (HFD) both exhibited increased HADHA expression. HADHA Heterozygous mice fed with HFD showed enhanced steatosis associated with a reduction of SCs assembly and OXPHOS function. The results indicate that HADHA participates in SCs assembly and couples FAO and OXPHOS. |
| format | Article |
| id | doaj-art-4a65a6e132004df783d3baf65f858ef1 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-4a65a6e132004df783d3baf65f858ef12024-12-18T14:18:10ZengWileyAdvanced Science2198-38442024-12-011147n/an/a10.1002/advs.202405147HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOSChaoying Qin0Shasha Gong1Ting Liang2Zhenbo Zhang3Jessie Thomas4Janice Deng5Yaguang Liu6Peiqing Hu7Bi Zhu8Shujie Song9Marisol Fernández Ortiz10Yuji Ikeno11Exing Wang12James Lechleiter13Susan T. Weintraub14Yidong Bai15Department of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USABarshop Institute of Aging Research and Longevity and Department of Pathology University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Biochemistry and Structural Biology The University of Texas Health San Antonio San AntonioTexas 78229 USADepartment of Cell Systems and Anatomy The University of Texas Health San Antonio San AntonioTexas 78229 USAAbstract Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are key bioenergetics pathways. The machineries for both processes are localized in mitochondria. Secondary OXPHOS defects have been documented in patients with primary FAO deficiencies, and vice versa. However, the underlying mechanisms remain unclear. Intrigued by the observations that regulation of supercomplexes (SCs) assembly in a mouse OXPHOS deficient cell line and its derivatives is associated with the changes in lipid metabolism, a proteomics analysis is carried out and identified mitochondrial trifunctional protein (MTP) subunit alpha (hydroxyacyl‐CoA dehydrogenase trifunctional multienzyme complex subunit alpha, HADHA) as a potential regulatory factor for SCs assembly. HADHA‐Knockdown cells and mouse embryonic fibroblasts (MEFs) derived from HADHA‐Knockout mice displayed both reduced SCs assembly and defective OXPHOS. Stimulation of OXPHOS induced in cell culture by replacing glucose with galactose and of lipid metabolism in mice with a high‐fat diet (HFD) both exhibited increased HADHA expression. HADHA Heterozygous mice fed with HFD showed enhanced steatosis associated with a reduction of SCs assembly and OXPHOS function. The results indicate that HADHA participates in SCs assembly and couples FAO and OXPHOS.https://doi.org/10.1002/advs.202405147fatty acid oxidation (FAO)HADHAmitochondrial respiratory chainmitochondrial trifunctional protein (MTP)respiratory complex I |
| spellingShingle | Chaoying Qin Shasha Gong Ting Liang Zhenbo Zhang Jessie Thomas Janice Deng Yaguang Liu Peiqing Hu Bi Zhu Shujie Song Marisol Fernández Ortiz Yuji Ikeno Exing Wang James Lechleiter Susan T. Weintraub Yidong Bai HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS Advanced Science fatty acid oxidation (FAO) HADHA mitochondrial respiratory chain mitochondrial trifunctional protein (MTP) respiratory complex I |
| title | HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS |
| title_full | HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS |
| title_fullStr | HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS |
| title_full_unstemmed | HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS |
| title_short | HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS |
| title_sort | hadha regulates respiratory complex assembly and couples fao and oxphos |
| topic | fatty acid oxidation (FAO) HADHA mitochondrial respiratory chain mitochondrial trifunctional protein (MTP) respiratory complex I |
| url | https://doi.org/10.1002/advs.202405147 |
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