Estrogen regulates spatially distinct cardiac mitochondrial subpopulations

Ribeiro, Rogério Faustino; Rodrigues, Paula; Morra, Elis Aguiar; Ronconi, Karoline Sousa; Lima, Patrícia Ribeiro Do Val; Porto, Marcella L.; Vassallo, Dalton Valentim; Figueiredo, Suely G.; Stefanon, Ivanita

doi:10.1016/j.mito.2017.05.011

Cited by 12 publications

(10 citation statements)

References 46 publications

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“…Our previous findings linked a direct effect of E2 on mitochondrial membrane viscosity to improved CI function in skeletal muscle (17). The extent to which a similar mechanism of action is present in other tissues is unclear, although E2-mediated increases in mitochondrial CI-supported JO 2 have been previously reported in other tissues with high CI-linked mitochondrial respiratory capacity, including brain (11) and cardiac muscle (37,38). The impact of E2 loss and replacement on liver mitochondrial function, however, appears to be comparatively modest and may simply reflect tissue-specific heterogeneity in inherent E2 content and/or varying dependence on membrane-bound estrogen receptor signaling (39,40).…”

Section: Estrogen and Complex I In Liver And Skeletal Musclementioning

confidence: 79%

Impact of 17β-estradiol on complex I kinetics and H2O2 production in liver and skeletal muscle mitochondria

Torres

Ryan

Lin

et al. 2018

Journal of Biological Chemistry

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Naturally or surgically induced postmenopausal women are widely prescribed estrogen therapies to alleviate symptoms associated with estrogen loss and to lower the subsequent risk of developing metabolic diseases, including diabetes and nonalcoholic fatty liver disease. However, the molecular mechanisms by which estrogens modulate metabolism across tissues remain ill-defined. We have previously reported that 17β-estradiol (E2) exerts antidiabetogenic effects in ovariectomized (OVX) mice by protecting mitochondrial and cellular redox function in skeletal muscle. The liver is another key tissue for glucose homeostasis and a target of E2 therapy. Thus, in the present study we determined the effects of acute loss of ovarian E2 and E2 administration on liver mitochondria. In contrast to skeletal muscle mitochondria, E2 depletion via OVX did not alter liver mitochondrial respiratory function or complex I (CI) specific activities (NADH oxidation, quinone reduction, and HO production). Surprisingly, E2 replacement therapy and E2 exposure induced tissue-specific effects on both CI activity and on the rate and topology of CI HO production. Overall, E2 therapy protected and restored the OVX-induced reduction in CI activity in skeletal muscle, whereas in liver mitochondria E2 increased CI HO production and decreased ADP-stimulated respiratory capacity. These results offer novel insights into the tissue-specific effects of E2 on mitochondrial function.

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Section: Estrogen and Complex I In Liver And Skeletal Musclementioning

confidence: 79%

Impact of 17β-estradiol on complex I kinetics and H2O2 production in liver and skeletal muscle mitochondria

Torres

Ryan

Lin

et al. 2018

Journal of Biological Chemistry

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“…Subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) were isolated as previously described [20] , [21] , [22] . Briefly, the LV was rinsed in ice cold Chappel-Perry buffer (100 mM KCl, 50 mM MOPS, 5 mM MgSO4, 1 mM ATP, 1 mM EGTA, 2 mg/mL BSA), blotted dry and then weighed.…”

Section: Methodsmentioning

confidence: 99%

“…Mitochondrial respiration was assessed in both IFM and SSM as described previously [21] , [23] . Isolated mitochondria (0.5 mg/mL) were respired in respiration buffer containing 100 mM KCl, 50 mM MOPS, 5 mM KH 2 PO 4 , 1 mM EGTA and 1 mg/mL BSA/Fraction V, using a polarographic oxygen sensing systems for measurements of dissolved oxygen consumption in liquid suspension (Qubit System, Kingston, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

“…Ca 2+ tolerance was evaluated according to previous reports [21] , [25] , [26] . Briefly, mitochondria were resuspended in swelling buffer [containing 100 mM KCl, 50 mM MOPS, 5 mM KH 2 PO 4 , 5 µM EGTA, 1 mM MgCl 2 , 5 mM glutamate, and 5 mM malate] at 2 mg/mL protein concentration and warmed to room temperature in a 96-well plate.…”

Section: Methodsmentioning

confidence: 99%

“…Hydrogen peroxide production in isolated mitochondrial subpopulations was determined using the oxidation of the fluorogenic indicator Amplex Red (Invitrogen) in the presence of horseradish peroxidase as previously described [21] . The concentrations of horseradish peroxidase and Amplex Red in the incubation were 0.1 unit/mL and 50 μM, respectively, and detection of fluorescence was assessed on a on a Molecular Devices Flex Station 3 fluorescence plate reader (Molecular Devices, Sunnyvale, CA) with 530-nm excitation and 590-nm emission wavelengths.…”

Section: Methodsmentioning

confidence: 99%

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MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload

Ribeiro

Dabkowski

Shekar

et al. 2018

Free Radical Biology and Medicine

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113

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Heart failure remains a major public-health problem with an increase in the number of patients worsening from this disease. Despite current medical therapy, the condition still has a poor prognosis. Heart failure is complex but mitochondrial dysfunction seems to be an important target to improve cardiac function directly.Our goal was to analyze the effects of MitoQ (100 µM in drinking water) on the development and progression of heart failure induced by pressure overload after 14 weeks. The main findings are that pressure overload-induced heart failure in rats decreased cardiac function in vivo that was not altered by MitoQ. However, we observed a reduction in right ventricular hypertrophy and lung congestion in heart failure animals treated with MitoQ. Heart failure also decreased total mitochondrial protein content, mitochondrial membrane potential in the intermyofibrillar mitochondria. MitoQ restored membrane potential in IFM but did not restore mitochondrial protein content. These alterations are associated with the impairment of basal and stimulated mitochondrial respiration in IFM and SSM induced by heart failure. Moreover, MitoQ restored mitochondrial respiration in heart failure induced by pressure overload. We also detected higher levels of hydrogen peroxide production in heart failure and MitoQ restored the increase in ROS production. MitoQ was also able to improve mitochondrial calcium retention capacity, mainly in the SSM whereas in the IFM we observed a small alteration. In summary, MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload, by decreasing hydrogen peroxide formation, improving mitochondrial respiration and improving mPTP opening.

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Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice

Pieronne-Deperrois

Gueret

Djerada³

et al. 2021

ESC Heart Failure

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Aims In post-menopausal women, incidence of heart failure with preserved ejection fraction is higher than in men. Hormonal replacement therapies did not demonstrate benefits. We tested whether the non-steroidal mineralocorticoid receptor antagonist finerenone limits the progression of heart failure in ovariectomized (OVX) mice with metabolic disorders. Methods and results Ovariectomy was performed in 4-month-old mice, treated or not at 7 months old for 1 month with finerenone (Fine) 1 mg/kg/day. Left ventricular (LV) cardiac and coronary endothelial functions were assessed by echocardiography, catheterization, and myography. Blood pressure was measured by plethysmography. Insulin and glucose tolerance tests were performed. Exercise capacity and spontaneous activity were measured on treadmill and in combined indirect calorimetric cages equipped with voluntary running wheel. OVX mice presented LV diastolic dysfunction without modification of ejection fraction compared with controls (CTL), whereas finerenone improved LV filling pressure (LV end-diastolic pressure, mmHg: CTL 3.48 ± 0.41, OVX 6.17 ± 0.30**, OVX + Fine 3.65 ± 0.55 † , **P < 0.01 vs. CTL, † P < 0.05 vs. OVX) and compliance (LV end-diastolic pressure-volume relation, mmHg/RVU: CTL 1.65 ± 0.42, OVX 4.77 ± 0.37***, OVX + Fine 2.87 ± 0.26 † † , ***P < 0.001 vs. CTL, † † P < 0.01 vs. OVX). Acetylcholine-induced endothelial-dependent relaxation of coronary arteries was impaired in ovariectomized mice and improved by finerenone (relaxation, %: CTL 86 ± 8, OVX 38 ± 3**, OVX + Fine 83 ± 7 † † , **P < 0.01 vs. CTL, † † P < 0.01 vs. OVX). Finerenone improved decreased ATP production by subsarcolemmal mitochondria after ovariectomy. Weight gain, increased blood pressure, and decreased insulin and glucose tolerance in OVX mice were improved by finerenone. The exercise capacity at race was diminished in untreated OVX mice only. Spontaneous activity measurements in ovariectomized mice showed decreased horizontal movements, reduced time spent in a running wheel, and reduced VO 2 and VCO 2 , all parameters improved by finerenone. Conclusions Finerenone improved cardiovascular dysfunction and exercise capacity after ovariectomy-induced LV diastolic dysfunction with preserved ejection fraction.

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Estrogen regulates spatially distinct cardiac mitochondrial subpopulations

Cited by 12 publications

References 46 publications

Impact of 17β-estradiol on complex I kinetics and H2O2 production in liver and skeletal muscle mitochondria

Impact of 17β-estradiol on complex I kinetics and H2O2 production in liver and skeletal muscle mitochondria

MitoQ improves mitochondrial dysfunction in heart failure induced by pressure overload

Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice

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