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Accumulation of depolarized mitochondria within beta-cells has been associated with oxidative damage and development of diabetes. To determine the source and fate of depolarized mitochondria, individual mitochondria were photolabeled and tracked through fusion and fission. Mitochondria were found to go through frequent cycles of fusion and fission in a(More)
SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a(More)
BACKGROUND The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR) may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this(More)
Congenital deficiency of the mitochondrial respiratory chain complex I (CI) is a common defect of oxidative phosphorylation (OXPHOS). Despite major advances in the biochemical and molecular diagnostics and the deciphering of CI structure, function assembly and pathomechanism, there is currently no satisfactory cure for patients with mitochondrial complex I(More)
OBJECTIVE The role of uncoupling protein 2 (UCP2) in pancreatic β-cells is highly debated, partly because of the broad tissue distribution of UCP2 and thus limitations of whole-body UCP2 knockout mouse models. To investigate the function of UCP2 in the β-cell, β-cell-specific UCP2 knockout mice (UCP2BKO) were generated and characterized. RESEARCH DESIGN(More)
OBJECTIVE beta-Cell response to glucose is characterized by mitochondrial membrane potential (Delta Psi) hyperpolarization and the production of metabolites that serve as insulin secretory signals. We have previously shown that glucose-induced mitochondrial hyperpolarization accompanies the concentration-dependent increase in insulin secretion within a wide(More)
1 OBJECTIVE—Previous studies have reported that ␤-cell mito-chondria exist as discrete organelles that exhibit heterogeneous bioenergetic capacity. To date, networking activity, and its role in mediating ␤-cell mitochondrial morphology and function, remains unclear. In this article, we investigate ␤-cell mitochon-drial fusion and fission in detail and(More)
Studies in various types of cells find that, on average, each mitochondrion becomes involved in a fusion event every 15 min, depending on the cell type. As most contact events do not result in mitochondrial fusion, it is expected that properties of the individual mitochondrion determine the likelihood of a fusion event. However, apart from membrane(More)
Assembly of mitochondria into networks supports fuel metabolism and calcium transport and is involved in the cellular response to apoptotic stimuli. A mitochondrial network is defined as a continuous matrix lumen whose boundaries limit molecular diffusion. Observation of individual networks has proven challenging in live cells that possess dense populations(More)
Concentrations of 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxy indoleacetic acid (5-HIAA) and homovanillic acid (HVA) were determined in lumbar cerebrospinal fluid (CSF) from control subjects and patients of both presenile and senile age with histologically verified Alzheimer's dementia. CSF HVA increased with age in control but not in Alzheimer(More)