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HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS
Chaoying Qin1,2, Shasha Gong1,3, Ting Liang1
1Department of Cell Systems and Anatomy, The University of Texas Health San Antonio, San Antonio, Texas, 78229, USA.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 3, 2024
Summary
Mitochondrial trifunctional protein subunit alpha (HADHA) regulates the assembly of supercomplexes (SCs) and couples fatty acid oxidation (FAO) with oxidative phosphorylation (OXPHOS). HADHA deficiency impairs both energy pathways, highlighting its crucial role in cellular bioenergetics.
Area of Science:
- Mitochondrial bioenergetics
- Cellular metabolism
- Proteomics
Background:
- Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are critical energy pathways localized in mitochondria.
- Secondary defects in OXPHOS and FAO are observed in patients, but mechanisms are unclear.
- Mitochondrial supercomplexes (SCs) assembly is linked to lipid metabolism.
Purpose of the Study:
- To investigate the role of mitochondrial trifunctional protein (MTP) subunit alpha (HADHA) in SCs assembly.
- To elucidate the coupling mechanisms between FAO and OXPHOS.
Main Methods:
- Proteomics analysis to identify regulatory factors.
- HADHA knockdown cells and knockout mouse embryonic fibroblasts (MEFs).
- Cell culture with galactose and high-fat diet (HFD) in mice.
Main Results:
- Proteomics identified HADHA as a potential regulator of SCs assembly.
- HADHA deficiency led to reduced SCs assembly and defective OXPHOS.
- Stimulating OXPHOS or lipid metabolism increased HADHA expression.
- HFD-fed HADHA heterozygous mice showed steatosis, reduced SCs assembly, and impaired OXPHOS.
Conclusions:
- HADHA is a key factor in mitochondrial supercomplex assembly.
- HADHA couples fatty acid oxidation and oxidative phosphorylation.
- HADHA plays a vital role in maintaining cellular energy homeostasis.
Keywords:
HADHAfatty acid oxidation (FAO)mitochondrial respiratory chainmitochondrial trifunctional protein (MTP)respiratory complex IMore Related Videos
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