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Steroidogenesis in MA-10 Mouse Leydig Cells Is Altered via Fatty Acid Import into the Mitochondria1
- Source :
- Biology of Reproduction. 91
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 2014.
-
Abstract
- Mitochondria are home to many cellular processes, including oxidative phosphorylation and fatty acid metabolism, and in steroid-synthesizing cells, they are involved in cholesterol import and metabolism, which is the initiating step in steroidogenesis. The formation of macromolecular protein complexes aids in the regulation and efficiency of these mitochondrial functions, though because of their dynamic nature, they are hard to identify. To overcome this problem, we used Blue-Native PAGE with whole-gel mass spectrometry on isolated mitochondria from control and hormone-treated MA-10 mouse tumor Leydig cells. The presence of multiple mitochondrial protein complexes was shown. Although these were qualitatively similar under control and human chorionic gonadotropin (hCG)-stimulated conditions, quantitative differences in the components of the complexes emerged after hCG treatment. A prominent decrease was observed with proteins involved in fatty acid import into the mitochondria, implying that mitochondrial beta-oxidation is not essential for steroidogenesis. To confirm this observation, we inhibited fatty acid import utilizing the CPT1a inhibitor etomoxir, resulting in increased steroid production. Conversely, stimulation of mitochondrial beta-oxidation with metformin resulted in a dose-dependent reduction in steroidogenesis. These changes were accompanied by changes in mitochondrial respiration and in the lactic acid formed during glycolysis. Taken together, these results suggest that upon hormonal stimulation, mitochondria efficiently import cholesterol for steroid production at the expense of other lipids necessary for energy production, specifically fatty acids required for beta-oxidation.
- Subjects :
- Male
Oxidative phosphorylation
Mitochondrion
Steroid biosynthesis
Biology
Cell Line
Mice
chemistry.chemical_compound
Animals
Hypoglycemic Agents
Beta oxidation
chemistry.chemical_classification
Fatty acid metabolism
Fatty Acids
Leydig Cells
Fatty acid
Biological Transport
Articles
Cell Biology
General Medicine
Metformin
Mitochondria
Cell biology
Gene Expression Regulation
Reproductive Medicine
chemistry
Cholesterol import
Biochemistry
Steroids
Transcriptome
Oxidation-Reduction
Etomoxir
Subjects
Details
- ISSN :
- 15297268 and 00063363
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Biology of Reproduction
- Accession number :
- edsair.doi.dedup.....34bf06a06505281628c42423a769d91d