Altered mitochondria-associated ER membrane (MAM) function shifts mitochondrial metabolism in amyotrophic lateral sclerosis (ALS).

Mitochondrial function is modulated by its interaction with the endoplasmic reticulum (ER). Recent research indicates that these contacts are disrupted in familial models of amyotrophic lateral sclerosis (ALS). We report here that this impairment in the crosstalk between mitochondria and the ER impedes the use of glucose-derived pyruvate as mitochondrial fuel, causing a shift to fatty acids to sustain energy production.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) have identified genetic loci that robustly associate with Alzheimer's Disease (AD), many of which are preferentially or exclusively expressed in innate immune cells. Among the identified AD risk genes is CD33: a transmembrane, sialic acid-binding protein expressed on the surface of myeloid cells including microglia, the innate immune cells of the CNS. The function of microglia is highly responsive to and regulated by metabolic changes, which allows them to rapidly change phenotype and maintain brain health.

CD33 and SHP-1/ Interaction in Alzheimer's Disease.

Large-scale genetic studies have identified numerous genetic risk factors that suggest a central role for innate immune cells in susceptibility to Alzheimer's disease (AD). CD33, an immunomodulatory transmembrane sialic acid binding protein expressed on myeloid cells, was identified as one such genetic risk factor associated with Alzheimer's disease. Several studies explored the molecular outcomes of genetic variation at the locus.

Size-frequency distributions and physical properties of chondrules from x-ray computed microtomography and digital data extraction.

Within this work, we present the first true three-dimensional (3D) analysis of chondrule size. Knowledge about the physical properties of chondrules is important for validating astrophysical theories concerning chondrule formation and their aggregation into the chondritic meteorites (known as chondrites) that contain them. The classification of chondrites into chemical groups also relies on chondrule properties, including their dimensions.

Assessing mitochondrial respiratory bioenergetics in whole cells and isolated organelles by microplate respirometry.

Mitochondria are responsible for the generation of ATP by oxidative phosphorylation; however, these multifaceted organelles regulate many other key cellular functions as well, such as calcium homeostasis, apoptosis, and biosynthesis of steroid hormones, heme and phospholipids. In order to carry out these functions, mitochondria establish physical and functional connections with other organelles such as the plasma membrane, lipid droplets/vesicles, peroxisomes, endosomes, and the endoplasmic reticulum. Dysregulation of any of the aforementioned processes or inter-organelle contacts can lead to mitochondrial dysfunction and subsequent changes in oxygen consumption and ATP production.

The dark side of browning.

The induction of brown-like adipocyte development in white adipose tissue (WAT) confers numerous metabolic benefits by decreasing adiposity and increasing energy expenditure. Therefore, WAT browning has gained considerable attention for its potential to reverse obesity and its associated co-morbidities. However, this perspective has been tainted by recent studies identifying the detrimental effects of inducing WAT browning.