Using mitochondrial respiration inhibitors to design a novel model of bipolar disorder-like phenotype with construct, face and predictive validity.

We mimicked mild mitochondrial-distress robustly reported in bipolar-disorder (BD) by chronic exposure to uniquely low doses of inhibitors of mitochondrial-respiration complexes in vitro and in vivo. Exposure of the neuronal-originating SH-SY5Y cells to very low dose (10 pM) rotenone, a mitochondrial-respiration complex (Co)I inhibitor, for 72 or 96 h did not affect cell viability and reactive oxygen species (ROS) levels. Yet, it induced a dual effect on mitochondrial-respiration: overshooting statistically significant several-fold increase of most oxygen-consumption-rate (OCR) parameters vs.

NCLX prevents cell death during adrenergic activation of the brown adipose tissue.

A sharp increase in mitochondrial Ca marks the activation of brown adipose tissue (BAT) thermogenesis, yet the mechanisms preventing Ca deleterious effects are poorly understood. Here, we show that adrenergic stimulation of BAT activates a PKA-dependent mitochondrial Ca extrusion via the mitochondrial Na/Ca exchanger, NCLX. Adrenergic stimulation of NCLX-null brown adipocytes (BA) induces a profound mitochondrial Ca overload and impaired uncoupled respiration.

MitoTimer-based high-content screen identifies two chemically-related benzothiophene derivatives that enhance basal mitophagy.

Mitochondrial turnover is required for proper cellular function. Both mitochondrial biogenesis and mitophagy are impaired in several degenerative and age-related diseases. The search for mitophagy activators recently emerged as a new therapeutical approach; however, there is a lack in suitable tools to follow mitochondrial turnover in a high-throughput manner.

Emerging roles of β-cell mitochondria in type-2-diabetes.

Type-2-Diabetes (T2D) is the most common metabolic disease in the world today. It erupts as a result of peripheral insulin resistance combined with hyperinsulinemia followed by suppression of insulin secretion from pancreatic β-cells. Mitochondria play a central role in β-cells by sensing glucose and also by mediating the suppression of insulin secretion in T2D.

Nanoparticle-mediated lysosomal reacidification restores mitochondrial turnover and function in β cells under lipotoxicity.

Chronic exposure of pancreatic β cells to high concentrations of free fatty acids leads to lipotoxicity (LT)-mediated suppression of glucose-stimulated insulin secretion. This effect is in part caused by a decline in mitochondrial function as well as by a reduction in lysosomal acidification. Because both mitochondria and lysosomes can alter one another's function, it remains unclear which initiating dysfunction sets off the detrimental cascade of LT, ultimately leading to β-cell failure.