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Background: Mitochondria are essential organelles with various functions, and change its network dynamically. The inner mitochondrial membrane (IMM) contains the cristae membrane (CM), which extends into mitochondrial matrix space. A loss of mitofilin, one of the main component of mitochondrial contact site and cristae organizing system (MICOS) complex in the IMM, has known to be unable to preserve CM structure, accompanied with lower membrane potential. And a disruption of mitoNEET, novel protein located in the outer mitochondrial membrane, has been shown to decrease mitochondrial membrane potential, however, the role of mitoNEET in structure of the CM has not been elucidated. Methods and Results: mitoNEET flox/flox mice were generated with lox-P and homologous recombination strategies. Cardiac-specific deletion of mitoNEET (mitoNEET-knockout) was achieved using αMHC-Cre. Transmission electron microscopy showed the mitochondria isolated from mitoNEET-knockout mice reduced number of cristae, loss of the cristae junctions, and accumulation of cristae stack. These mitochondria also exhibited a swollen morphology. ROS production from the mitochondria were higher in mitoNEET-knockout mice. Mitochondrial state 3 respirations were comparable between the groups, however, mitochondrial maximal capacity and reserve capacity in mitoNEET-knockout mice. Mitochondrial membrane potential measured by using cultured cells transfected with CISD1 , encoding mitoNEET, siRNA was decreased in this condition compared to scramble. Mass spectrometry analysis revealed that endogenous mitoNEET coprecipitated with endogenous mitofilin, which is known to be localized in the IMM and involved in CM structure. Echocardiography showed cardiac dysfunction in mitoNEET-knockout mice. Conclusions: The protein-protein interaction between mitoNEET and mitofilin may regulate CM structure through the maintenance of MICOS complex including mitofilin. The lack of this interaction could induce mitochondrial dysfunction, suggesting that mitoNEET play an important role in the regulation of mitochondrial function via mitochondrial morphology. [ABSTRACT FROM AUTHOR]

The article presents the study which examines how brain-derived neurotrophic factor (rhBDNF) improved limited exercise capacity in mice with heart failure. It offers details of the study which involved induction of a myocardial infarction (MI) in 10- to 12-week-old male mice by ligating the coronary artery.

The article reports on research which was conducted to investigate intramuscular metabolic responses during low-intensity resistance exercise with blood flow restriction (BFR) exercise between two different types of track athletes. Researchers evaluated 12 age matched track athletes who were either sprinters or endurance runners. They found that blood flow restriction (BFR) remarkably enhances muscular metabolic stress in resistance exercise, although there is a wide range of individual differences in the responses.

Introduction: Reduced exercise capacity is an independent predictor of poor prognosis in heart failure (HF) patients and is closely associated with skeletal muscle abnormalities including impaired mitochondrial dysfunction. We showed that mitochondrial function is impaired in skeletal muscle from HF mice at the chronic phase. This abnormality is known to be caused by increased reactive oxygen species (ROS) in HF. The pathogenic mechanism of mitochondrial dysfunction in association with increased ROS in skeletal muscle from HF is unclear. Xanthine oxidase (XO) was reported to be an important mediator of ROS overproduction in ischemic tissue because XO activates by hypoxia. Here we examined the role of XO-derived ROS in the regulation of mitochondrial function in skeletal muscle from mice with HF after myocardial infarction (MI). Methods and Results: MI was created in male C57BL/6J mice by ligating the left coronary artery, and a sham operation was also performed in survivors (n=8/group). Cardiac function measured by echocardiography was significantly decreased in the MI mice compared to the sham mice. We first examined whether XO-derived ROS evaluated by hydrogen peroxide production in skeletal muscle was increased in HF mice post-MI. The production of XO-derived ROS was significantly increased in the MI mice from 1 to 7 days post-surgery, whereas it did not differ between both groups at 14 and 28 days. Next, we divided mice into three groups in survivors (n=8/group): sham+vehicle, MI+vehicle, and MI+Feb (febuxostat, an XO inhibitor, 5 mg/kg body weight/day). Feb or vehicle was administered by oral gavage at 1 and 24 h before and once-daily on days 1 to 7 post-MI or sham surgery. At day 28 post-surgery, exercise capacity as evaluated by treadmill testing and the mitochondrial respiration in skeletal muscle fibers shown by high-resolution respirometry were significantly decreased in the MI mice compared to the sham mice, and these were preserved in the MI+Feb mice in association with decreased XO-derived ROS. The chronic (28-day) administration of Feb did not preserve these favorable outcomes. Conclusion: XO inhibition during increased XO-derived ROS in the acute phase can preserve mitochondrial function in skeletal muscle and exercise capacity in HF mice. [ABSTRACT FROM AUTHOR]

Introduction: Mitochondrial dysfunction and oxidative stress play a crucial role in the development of heart failure. However, the role of reactive oxygen species (ROS) originating from peripheral blood mononuclear cell (PBMC) mitochondria in chronic heart failure (HF) is unknown. Hypothesis: Mitochondrial ROS emission from PBMCs is increased in symptomatic HF patients, which is linked to systemic oxidative stress, HF severity, and exercise intolerance. Methods: We enrolled 36 patients with chronic HF (62 ± 13 years, New York Heart Association [NYHA] functional class I-III) and the patients were divided into two groups; NYHA I-II group (n=17) and NYHA III group (n=19). To assess exercise capacity, we performed cardiopulmonary exercise testing with bicycle ergometer. We measured mitochondrial respiratory capacity and mitochondrial ROS emission in permeabilized PBMCs with the use of high-resolution respirometry and spectrofluorometry. We also measured urine 8-OHdG as a marker of systemic oxidative stress. Results: Plasma levels of B-type natriuretic peptide (BNP), a biomarker for severity of HF, were significantly higher in NYHA III group than in NYHA I-II group (286.0±251.0 vs. 93.4±101.2 pg/mL, P <0.01). HF patients with NYHA III had a lowered peak oxygen uptake (VO2) compared to HF patients with NYHA I-II (14.4±4.1 vs. 19.7±4.5 mL/kg/min, P <0.01). Mitochondrial oxidative phosphorylation capacities with complex I, complex II, or complex I+II-linked substrates in PBMCs were comparable between groups, however, maximal capacity of mitochondrial electron transfer system with complex II-linked substrates in PBMCs was significantly reduced in NYHA III group in association with the lowered peak VO2. Notably, HF patients with NYHA III had a significantly higher mitochondrial ROS emission from PBMCs, and this was closely correlated with the elevated urine 8-OHdG levels, the increased plasma levels of BNP, and the lowered peak VO2, respectively. Conclusions: Increased mitochondrial ROS emission in circulating PBMCs is associated with systemic oxidative stress, HF severity, and exercise intolerance in patients with chronic HF. [ABSTRACT FROM AUTHOR]