Drosophila tweety facilitates autophagy to regulate mitochondrial homeostasis and bioenergetics in Glia.

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal defects were partially reversed by antioxidant treatment. We performed live-cell imaging of genetically encoded metabolite sensors to determine the impact of tty and autophagy deficiencies on glial bioenergetics. We found that tty-deficient glia exhibited reduced mitochondrial pyruvate consumption accompanied by a shift toward glycolysis for ATP production. Likewise, genetic inhibition of autophagy in glia resulted in a similar glycolytic shift in bioenergetics. Furthermore, the survival of mutant flies became more sensitive to starvation, underlining the significance of tty in the crosstalk between autophagy and bioenergetics. Together, our findings uncover the role for tty in mitochondrial homeostasis via facilitating autophagy, which determines bioenergetic balance in glia.

The RVEIO and RV function: More, please.

Early proof of the value of RVEIO is currently limited by acquisition biases in specific patient populations. More research is needed on this potentially important index.

Social Media as a Tool to Advance Women in Cardiology: Paving the Way for Gender Equality and Diversity.

Although the number of women in the field of medicine continues to rise, the discrimination against women and the gender inequity in both leadership roles and salary remains persistent. The gender divide is particularly prominent in male-dominated specialties, such as cardiology. Social media help foster global connections and disseminate information quickly and worldwide. The rise of social media has influenced how female physicians communicate and has shown its benefits particularly within the field of cardiology. Virtual platforms are important avenues where female physicians have united for greater representation of gender issues and advocacy efforts. Social media further amplify gender-equality activism by facilitating the conversations surrounding gender equity and proposing solutions to self-identified issues by the virtual community of female physicians and their allies. In this review, we discuss the role of social media as tools for advancing women in the field of cardiology and fostering gender equality and diversity.

Bien que le nombre de femmes dans le domaine de la médecine continue d'augmenter, la discrimination à l'égard des femmes et l'inégalité entre les sexes, tant au niveau des rôles de direction que des salaires, persistent. L'écart entre les sexes est particulièrement marqué dans les spécialités à prédominance masculine, comme la cardiologie. Les médias sociaux contribuent à favoriser les liens à l'échelle mondiale et permettent de diffuser des renseignements rapidement dans le monde entier. L'essor des médias sociaux a influencé la manière dont les femmes médecins communiquent, et ces médias ont démontré des bienfaits, notamment dans le domaine de la cardiologie. Les plateformes virtuelles sont des moyens importants utilisés par les femmes médecins pour s'unir afin de mieux mettre de l'avant les questions de genre et d'améliorer les efforts de sensibilisation. Les médias sociaux amplifient encore davantage le militantisme en faveur de l'égalité des sexes en facilitant les conversations autour de l'égalité des sexes et en proposant des solutions aux problèmes ciblés par la communauté virtuelle des femmes médecins et de leurs alliés. Dans cet examen, nous discutons du rôle des médias sociaux à titre d'outils permettant de faire progresser les femmes dans le domaine de la cardiologie et de favoriser l'égalité des sexes et la diversité.

(-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: underlying mechanisms.

The consumption of cocoa products rich in (-)-epicatechin is associated with reduced cardiovascular risk and improved vascular function. However, little is known about (-)-epicatechin's effects on aged endothelium. In order to characterize the health restoring effects of (-)-epicatechin on aged endothelium and identify the underlying mechanisms, we utilized high passage number (i.e. aged) bovine coronary artery endothelial cells and aortas of 3 and 18 month old rats. We evaluated cell senescence (ß-galactosidase), nitric oxide (NO) production through the endothelial nitric oxide synthase pathway, mitochondria related endpoints, citrate synthase activity and vascular relaxation. Cells were treated with water or (-)-epicatechin (1 µM) for 48 h and rats orally with either water or (-)-epicatechin (1 mg kg-1 day-1) for 15 days. Senescence associated ß-galactosidase levels doubled in aged cells while those treated with (-)-epicatechin only evidenced an ∼40% increase. NO levels in cells decreased by ∼33% with aging and (-)-epicatechin normalized them. Endothelial nitric oxide synthase phosphorylation levels paralleled these results. Aging increased total protein and synthase acetylation levels and (-)-epicatechin partially restored them to those of young cells by stimulating sirtuin-1 binding to the synthase. Phosphorylated sirtuin-1, mitofilin, oxidative phosphorylation complexes and transcriptional factor for mitochondria were reduced by ∼40% with aging and were restored by (-)-epicatechin. (-)-Epicatechin enhanced acetylcholine induced aged aorta vasodilation and stimulated NO levels while reducing blood pressure. In conclusion, (-)-epicatechin reverses endothelial cell aging and restores key control elements of vascular function. These actions may partly explain the epidemiological evidence for the beneficial effects of cocoa consumption on the incidence of cardiac and vascular diseases.

(-)-Epicatechin stimulates mitochondrial biogenesis and cell growth in C2C12 myotubes via the G-protein coupled estrogen receptor.

We have reported on the capacity of (-)-epicatechin ((-)-EPI) to stimulate mitochondrial biogenesis (MiB) in mouse skeletal muscle (SkM). However, the mechanisms mediating the effects of (-)-EPI are not fully understood. We previously identified a role of the G-protein coupled estrogen receptor (GPER) in modulating the vascular effects of (-)-EPI. We therefore tested the hypothesis that GPER mediates (at least in part) the stimulatory effects of (-)-EPI on MiB in SkM cells. As an in vitro model, we employed mouse SkM-derived C2C12 myoblasts differentiated into myotubes. Using confocal microscopy, we detected GPER at the cell surface and cytoplasm in C2C12 myotubes. Treatment with (-)-EPI (3 and 10µM) resulted in the stimulation of MiB as per increases in mitochondrial inner (MitoTracker Red FM fluorescence staining) and outer membrane (porin protein levels) markers, transcription factors involved in MiB stimulation (i.e., nuclear respiratory factor-2 [NRF-2] and mitochondrial transcription factor A [TFAM] protein levels) and citrate synthase (CS) activity levels. (-)-EPI-treated myotubes were longer and wider compared to vehicle-treated myotubes. The effects of (-)-EPI on myotube mitochondria and cell size were larger in magnitude to those observed with the GPER agonist G-1. The chemical blockade and down-regulation (siRNA) of GPER evidenced a partial and complete blockade of measured endpoints following (-)-EPI- or G-1-treatment, respectively. Altogether, results indicate that GPER is expressed in muscle cells and appears to mediate to a significant extent, the stimulatory effects of (-)-EPI on MiB. Thus, GPER activation may account for the stimulatory effects of (-)-EPI on SkM structure/function.

Browning effects of (-)-epicatechin on adipocytes and white adipose tissue.

In this study, we demonstrate that (-)-epicatechin (Epi), a cacao flavanol, induces the browning of fat by promoting mitochondrial biogenesis, enhancing indicators of mitochondrial structure and function, increasing fatty acid metabolism and upregulating the expression of brown adipose tissue-specific proteins in a high-fat diet mouse model of obesity and in cultured human adipocytes. Epi treatment significantly improved mitochondrial function, as measured by citrate synthase activity, and also reduced protein acetylation of total and specific regulators in both adipose tissue and human adipocytes. Browning of fat via Epi was evidenced by the increased expression of key thermogenic genes, phosphorylation of upstream regulators of fatty acid oxidation, and reduced triglyceride levels. Properly designed clinical trials are needed to explore the potential of Epi as an agent that promotes the browning of fat.