Lim 2018 Sci Rep
Lim SC, Tajika M, Shimura M, Carey KT, Stroud DA, Murayama K, Ohtake A, McKenzie M (2018) Loss of the mitochondrial fatty acid ฮฒ-oxidation protein medium-chain acyl-Coenzyme A dehydrogenase disrupts oxidative phosphorylation protein complex stability and function. Sci Rep 8:153. |
Lim SC, Tajika M, Shimura M, Carey KT, Stroud DA, Murayama K, Ohtake A, McKenzie M (2018) Sci Rep
Abstract: Medium-chain acyl-Coenzyme A dehydrogenase (MCAD) is involved in the initial step of mitochondrial fatty acid ฮฒ-oxidation (FAO). Loss of function results in MCAD deficiency, a disorder that usually presents in childhood with hypoketotic hypoglycemia, vomiting and lethargy. While the disruption of mitochondrial fatty acid metabolism is the primary metabolic defect, secondary defects in mitochondrial oxidative phosphorylation (OXPHOS) may also contribute to disease pathogenesis. Therefore, we examined OXPHOS activity and stability in MCAD-deficient patient fibroblasts that have no detectable MCAD protein. We found a deficit in mitochondrial oxygen consumption, with reduced steady-state levels of OXPHOS complexes I, III and IV, as well as the OXPHOS supercomplex. To examine the mechanisms involved, we generated an MCAD knockout (KO) using human 143B osteosarcoma cells. These cells also exhibited defects in OXPHOS complex function and steady-state levels, as well as disrupted biogenesis of newly-translated OXPHOS subunits. Overall, our findings suggest that the loss of MCAD is associated with a reduction in steady-state OXPHOS complex levels, resulting in secondary defects in OXPHOS function which may contribute to the pathology of MCAD deficiency. โข Keywords: 143B humman osteosarcoma cells โข Bioblast editor: Kandolf G โข O2k-Network Lab: AU Clayton St John J
Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression
Pathology: Cancer
Organism: Human Tissue;cell: Other cell lines Preparation: Intact cells Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Supercomplex
Coupling state: ET
HRR: Oxygraph-2k
2018-02