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Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells
- Source :
- American Journal of Physiology-Lung Cellular and Molecular Physiology. 308:L953-L961
- Publication Year :
- 2015
- Publisher :
- American Physiological Society, 2015.
-
Abstract
- Because of the many energy-demanding functions they perform and their physical location in the lung, alveolar epithelial type II (ATII) cells have a rapid cellular metabolism and the potential to influence substrate availability and bioenergetics both locally in the lung and throughout the body. A thorough understanding of ATII cell metabolic function in the healthy lung is necessary for determining how metabolic changes may contribute to pulmonary disease pathogenesis; however, lung metabolism is poorly understood at the cellular level. Here, we examine lactate utilization by primary ATII cells and the ATII model cell line, MLE-15, and link lactate consumption directly to mitochondrial ATP generation. ATII cells cultured in lactate undergo mitochondrial respiration at near-maximal levels, two times the rates of those grown in glucose, and oxygen consumption under these conditions is directly linked to mitochondrial ATP generation. When both lactate and glucose are available as metabolic substrate, the presence of lactate alters glucose metabolism in ATII to favor reduced glycolytic function in a dose-dependent manner, suggesting that lactate is used in addition to glucose when both substrates are available. Lactate use by ATII mitochondria is dependent on monocarboxylate transporter (MCT)-mediated import, and ATII cells express MCT1, the isoform that mediates lactate import by cells in other lactate-consuming tissues. The balance of lactate production and consumption may play an important role in the maintenance of healthy lung homeostasis, whereas disruption of lactate consumption by factors that impair mitochondrial metabolism, such as hypoxia, may contribute to lactic acid build-up in disease.
- Subjects :
- Monocarboxylic Acid Transporters
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Bioenergetics
Physiology
Cellular respiration
Cell Respiration
Mitochondrion
Carbohydrate metabolism
Cell Line
Mice
Oxygen Consumption
Lactate oxidation
Physiology (medical)
Internal medicine
medicine
Animals
Glycolysis
Lactic Acid
Monocarboxylate transporter
Symporters
biology
Epithelial Cells
Articles
Cell Biology
Metabolism
respiratory system
Carbon
Cell Hypoxia
Mitochondria
Mice, Inbred C57BL
Pulmonary Alveoli
Glucose
Endocrinology
biology.protein
Energy Metabolism
Subjects
Details
- ISSN :
- 15221504 and 10400605
- Volume :
- 308
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Lung Cellular and Molecular Physiology
- Accession number :
- edsair.doi.dedup.....08672b72ed7ddb12b6e32bb00dcb4208