Lower oxygen consumption and Complex I activity in mitochondria isolated from skeletal muscle of fetal sheep with intrauterine growth restriction
| Autor: | Sean W. Limesand, Andrew T. Antolic, Amy C. Kelly, Kevin Doubleday, Alexander L. Pendleton, Miranda J. Anderson, Ronald M. Lynch, Leticia E. Camacho, Paul R. Langlais, Melissa A. Davis |
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| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Physiology Endocrinology Diabetes and Metabolism Hamstring Muscles 0302 clinical medicine Pregnancy IDH3B Succinate-CoA Ligases Hypoxia reproductive and urinary physiology Fetal Growth Retardation biology Chemistry Electron Transport Complex II NADH dehydrogenase Isocitrate Dehydrogenase Up-Regulation medicine.anatomical_structure Isocitrate dehydrogenase embryonic structures OGDH Female Oxoglutarate dehydrogenase complex Research Article medicine.medical_specialty Citric Acid Cycle Down-Regulation Oxidative phosphorylation Electron Transport Complex IV Mitochondrial Proteins 03 medical and health sciences Oxygen Consumption Physiology (medical) Internal medicine medicine Animals Ketoglutarate Dehydrogenase Complex Muscle Skeletal Electron Transport Complex I Sheep Skeletal muscle Placental Insufficiency Hypoglycemia Mitochondria Muscle Citric acid cycle 030104 developmental biology Endocrinology biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Am J Physiol Endocrinol Metab |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00057.2020 |
| Popis: | Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower hindlimb oxygen consumption rates (OCRs), indicating depressed mitochondrial oxidative phosphorylation capacity in their skeletal muscle. We hypothesized that OCRs are lower in skeletal muscle mitochondria from IUGR fetuses, due to reduced electron transport chain (ETC) activity and lower abundances of tricarboxylic acid (TCA) cycle enzymes. IUGR sheep fetuses ( n = 12) were created with mid-gestation maternal hyperthermia and compared with control fetuses ( n = 12). At 132 ± 1 days of gestation, biceps femoris muscles were collected, and the mitochondria were isolated. Mitochondria from IUGR muscle have 47% lower State 3 (Complex I-dependent) OCRs than controls, whereas State 4 (proton leak) OCRs were not different between groups. Furthermore, Complex I, but not Complex II or IV, enzymatic activity was lower in IUGR fetuses compared with controls. Proteomic analysis ( n = 6/group) identified 160 differentially expressed proteins between groups, with 107 upregulated and 53 downregulated mitochondria proteins in IUGR fetuses compared with controls. Although no differences were identified in ETC subunit protein abundances, abundances of key TCA cycle enzymes [isocitrate dehydrogenase (NAD+) 3 noncatalytic subunit β (IDH3B), succinate-CoA ligase ADP-forming subunit-β (SUCLA2), and oxoglutarate dehydrogenase (OGDH)] were lower in IUGR mitochondria. IUGR mitochondria had a greater abundance of a hypoxia-inducible protein, NADH dehydrogenase 1α subcomplex 4-like 2, which is known to incorporate into Complex I and lower Complex I-mediated NADH oxidation. Our findings show that mitochondria from IUGR skeletal muscle adapt to hypoxemia and hypoglycemia by lowering Complex I activity and TCA cycle enzyme concentrations, which together, act to lower OCR and NADH production/oxidation in IUGR skeletal muscle. |
| Databáze: | OpenAIRE |
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