Torres 2018 Cell Metab

Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, Neufer PD (2018) 17β-estradiol directly lowers mitochondrial membrane microviscosity and improves bioenergetic function in skeletal muscle. Cell Metab 27:167-79. https://doi.org/10.1016/j.cmet.2017.10.003

» PMID: 29103922

Torres MJ, Kew KA, Ryan TE, Pennington ER, Lin CT, Buddo KA, Fix AM, Smith CA, Gilliam LA, Karvinen S, Lowe DA, Spangenburg EE, Zeczycki TN, Shaikh SR, Neufer PD (2018) Cell Metab

Abstract: 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 H₂O₂ emitting potential, whereas E2 administration in vivo and in vitro restored membrane E2 content, microviscosity, complex I and I + III activities, H₂O₂ 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. • Keywords: Estrogen, Hormone replacement therapy, Hydrogen peroxide, Insulin resistance, Membrane viscosity, Menopause, Mitochondria, Ovariectomy, Buffer Z, Blebbistatin, Amplex UltraRed • Bioblast editor: Kandolf G • O2k-Network Lab: US NC Greenville Neufer PD

Correction: FADH₂ and S-pathway

FADH₂ is shown as the substrate feeding electrons into the membrane-ETS in the S-pathway. This requires correction: "Whereas reduced NADH is a substrate of Complex I linked to dehydrogenases of the TCA cycle and mt-matrix upstream of CI, reduced FADH₂ is a product of Complex II with downstream electron flow from CII to Q" (page 48 in Ref [1]. For details see Ref [2].

1. Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002
2. Gnaiger E (2023) Complex II ambiguities ― FADH₂ in the electron transfer system. MitoFit Preprints 2023.3.v4. https://doi.org/10.26124/mitofit:2023-0003.v4

Labels: MiParea: Respiration, mt-Medicine, Pharmacology;toxicology  Pathology: Diabetes 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, CIV, NS, ROX  HRR: Oxygraph-2k 

2018-01