17β-Estradiol Directly Lowers Mitochondrial Membrane Microviscosity and Improves Bioenergetic Function in Skeletal Muscle
| Autor: | Cheryl A.S. Smith, Terence E. Ryan, Katherine A. Buddo, Sira Karvinen, Kimberly A. Kew, Tonya N. Zeczycki, Dawn A. Lowe, P. Darrell Neufer, Saame Raza Shaikh, Espen E. Spangenburg, Maria J. Torres, Laura A. A. Gilliam, Edward Ross Pennington, Amy Fix, Chien Te Lin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Physiology Cell Respiration Oxidative phosphorylation Mitochondrion Biology Article Energy homeostasis Diabetes Mellitus Experimental Electron Transport Microviscosity 03 medical and health sciences Insulin resistance Internal medicine medicine Animals Homeostasis Respiratory function Obesity Muscle Skeletal Inner mitochondrial membrane Molecular Biology Adiposity Electron Transport Complex I Estradiol Viscosity Ovary Skeletal muscle Cell Biology medicine.disease Mitochondria Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology medicine.anatomical_structure Cellular Microenvironment Mitochondrial Membranes Female Energy Metabolism Oxidation-Reduction |
| Zdroj: | Cell Metabolism. 27:167-179.e7 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2017.10.003 |
| Popis: | Summary Menopause results in a progressive decline in 17β-estradiol (E2) levels, increased adiposity, decreased insulin sensitivity, and a higher risk for type 2 diabetes. Estrogen therapies can help reverse these effects, but the mechanism(s) by which E2 modulates susceptibility to metabolic disease is not well understood. In young C57BL/6N mice, short-term ovariectomy decreased—whereas E2 therapy restored—mitochondrial respiratory function, cellular redox state (GSH/GSSG), and insulin sensitivity in skeletal muscle. E2 was detected by liquid chromatography-mass spectrometry in mitochondrial membranes and varied according to whole-body E2 status independently of ERα. Loss of E2 increased mitochondrial membrane microviscosity and H 2 O 2 emitting potential, whereas E2 administration in vivo and in vitro restored membrane E2 content, microviscosity, complex I and I + III activities, H 2 O 2 emitting potential, and submaximal OXPHOS responsiveness. These findings demonstrate that E2 directly modulates membrane biophysical properties and bioenergetic function in mitochondria, offering a direct mechanism by which E2 status broadly influences energy homeostasis. |
| Databáze: | OpenAIRE |
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