Dimming the Powerhouse: Mitochondrial Dysfunction in the Liver and Skeletal Muscle of Intrauterine Growth Restricted Fetuses
| Autor: | Sean W. Limesand, Ronald M. Lynch, Stephanie R. Wesolowski, Alexander L. Pendleton, Timothy R. H. Regnault |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Mitochondrial Diseases mitochondrial metabolism Endocrinology Diabetes and Metabolism Intrauterine growth restriction Review Mitochondrion S Phase Endocrinology 0302 clinical medicine Pregnancy Gene Expression Regulation Fungal reproductive and urinary physiology Fetal Growth Retardation Mitochondria tricarboxylic acid (TCA) cycle medicine.anatomical_structure Liver intrauterine growth restriction (IUGR) embryonic structures Female medicine.medical_specialty Molecular Sequence Data Citric Acid Cycle oxidative phosphorylation Oxidative phosphorylation Placental insufficiency Biology Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences Internal medicine Schizosaccharomyces medicine Animals Humans placental insufficiency Muscle Skeletal Base Sequence Catabolism G1 Phase Infant Newborn Skeletal muscle Metabolism medicine.disease RC648-665 Oxygen Citric acid cycle 030104 developmental biology 030217 neurology & neurosurgery |
| Zdroj: | Frontiers in Endocrinology, Vol 12 (2021) Frontiers in Endocrinology Paediatrics Publications |
| ISSN: | 1664-2392 |
| Popis: | Intrauterine growth restriction (IUGR) of the fetus, resulting from placental insufficiency (PI), is characterized by low fetal oxygen and nutrient concentrations that stunt growth rates of metabolic organs. Numerous animal models of IUGR recapitulate pathophysiological conditions found in human fetuses with IUGR. These models provide insight into metabolic dysfunction in skeletal muscle and liver. For example, cellular energy production and metabolic rate are decreased in the skeletal muscle and liver of IUGR fetuses. These metabolic adaptations demonstrate that fundamental processes in mitochondria, such as substrate utilization and oxidative phosphorylation, are tempered in response to low oxygen and nutrient availability. As a central metabolic organelle, mitochondria coordinate cellular metabolism by coupling oxygen consumption to substrate utilization in concert with tissue energy demand and accretion. In IUGR fetuses, reducing mitochondrial metabolic capacity in response to nutrient restriction is advantageous to ensure fetal survival. If permanent, however, these adaptations may predispose IUGR fetuses toward metabolic diseases throughout life. Furthermore, these mitochondrial defects may underscore developmental programming that results in the sequela of metabolic pathologies. In this review, we examine how reduced nutrient availability in IUGR fetuses impacts skeletal muscle and liver substrate catabolism, and discuss how enzymatic processes governing mitochondrial function, such as the tricarboxylic acid cycle and electron transport chain, are regulated. Understanding how deficiencies in oxygen and substrate metabolism in response to placental restriction regulate skeletal muscle and liver metabolism is essential given the importance of these tissues in the development of later lifer metabolic dysfunction. |
| Databáze: | OpenAIRE |
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