Lim 2018 Sci Rep

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Lim SC, Tajika M, Shimura M, Carey KT, Stroud DA, Murayama K, Ohtake A, McKenzie M (2018) Loss of the mitochondrial fatty acid β-oxidation protein medium-chain acyl-Coenzyme A dehydrogenase disrupts oxidative phosphorylation protein complex stability and function. Sci Rep 8:153.

» PMID: 29317722 Open Access

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 β-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.

Keywords: 143B humman osteosarcoma cells Bioblast editor: Kandolf G 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