Incorporating Mitochondrial Gene Expression Changes Within a Testable Mathematical Model for Alzheimer's Disease: Stress Response Modulation Predicts Potential Therapeutic Targets.

Background: Alzheimer's disease is a specific form of dementia characterized by the aggregation of amyloid-β plaques and tau tangles. New research has found that the formation of these aggregates occurs after dysregulation of cellular respiration and the production of radical oxygen species. Proteomic data shows that these changes are also related to unique gene expression patterns.

Expression Changes in Mitochondrial Genes Affecting Mitochondrial Morphology, Transmembrane Potential, Fragmentation, Amyloidosis, and Neuronal Cell Death Found in Brains of Alzheimer's Disease Patients.

Background: Alzheimer's disease (AD) is a neurological disease that has both a genetic and non-genetic origin. Mitochondrial dysfunction is a critical component in the pathogenesis of AD as deficits in oxidative capacity and energy production have been reported.

Objective: Nuclear-encoded mitochondrial genes were studied in order to understand the effects of mitochondrial expression changes on mitochondrial function in AD brains.

The T9861C Mutation in the mtDNA-Encoded Cytochrome C Oxidase Subunit III Gene Occurs in High Frequency but with Unequal Distribution in the Alzheimer's Disease Brain.

Mitochondrial dysfunction is recognized as a critical component in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Deficits in oxidative capacity and, specifically, cytochrome c oxidase (CO) activity have been reported in AD brains and platelets. We previously identified a point mutation at np 9861 in AD brain mitochondrial DNA (mtDNA) that alters amino acid 219 of subunit III of CO from phenylalanine to leucine.

Mitochondrial function and abnormalities implicated in the pathogenesis of ASD.

Mitochondria are the powerhouse that generate over 90% of the ATP produced in cells. In addition to its role in energy production, the mitochondrion also plays a major role in carbohydrate, fatty acid, amino acid and nucleotide metabolism, programmed cell death (apoptosis), generation of and protection against reactive oxygen species (ROS), immune response, regulation of intracellular calcium ion levels and even maintenance of gut microbiota. With its essential role in bio-energetic as well as non-energetic biological processes, it is not surprising that proper cellular, tissue and organ function is dependent upon proper mitochondrial function.

Reproductive competency and mitochondrial variation in aged Syrian hamster oocytes.

The hamster is a useful model of human reproductive biology because its oocytes are similar to those in humans in terms of size and structural stability. In the present study we evaluated fecundity rate, ovarian follicular numbers, ova production, mitochondrial number, structure and function, and cytoplasmic lamellae (CL) in young (2-4 months) and old (12-18 months) Syrian hamsters (Mesocricetus auratus). Young hamsters had higher fertilisation rates and larger litters than old hamsters (100 vs 50% and 9.

Endometriosis may be associated with mitochondrial dysfunction in cumulus cells from subjects undergoing in vitro fertilization-intracytoplasmic sperm injection, as reflected by decreased adenosine triphosphate production.

Objective: To determine whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa [GC]) cells of subjects undergoing IVF-intracytoplasmic sperm injection (ICSI).

Design: Prospective cohort study.

Setting: An IVF clinic in a tertiary academic care center.

Age-associated metabolic and morphologic changes in mitochondria of individual mouse and hamster oocytes.

Background: In human oocytes, as in other mammalian ova, there is a significant variation in the pregnancy potential, with approximately 20% of oocyte-sperm meetings resulting in pregnancies. This frequency of successful fertilization decreases as the oocytes age. This low proportion of fruitful couplings appears to be influenced by changes in mitochondrial structure and function.

The association of reproductive senescence with mitochondrial quantity, function, and DNA integrity in human oocytes at different stages of maturation.

Objective: To determine the impact of reproductive aging on oocyte mitochondrial quantity, function, and DNA (mtDNA) integrity.

Design: Prospective observational study.

Setting: IVF clinic in a tertiary academic care center.

Estrogen receptor alpha (ERalpha) phospho-serine-118 is highly expressed in human uterine leiomyomas compared to matched myometrium.

It is thought that the growth of uterine leiomyomas may be mediated by the interaction of estrogen receptor alpha (ERalpha) and growth factor pathways and that phosphorylation of ERalpha at serine 118 (ERalpha-phospho-Ser118) is important in this interaction. In this study, immunoblotting and immunohistochemistry were used to investigate the expression of ERalpha-phospho-Ser118, phosphorylated p44/42 mitogen-activated protein kinase (phospho-p44/42 MAPK), and proliferating cell nuclear antigen (PCNA) in human leiomyoma and myometrial tissues during the proliferative and secretory phases of the menstrual cycle. We found that tumors taken from the proliferative phase expressed significantly higher levels of ERalpha-phospho-Ser118, phospho-p44/42 MAPK, and PCNA compared to patient-matched myometria and had significantly higher ERalpha-phospho-Ser118 and PCNA expression compared to secretory phase tumors.

Mutations in mitochondrial-encoded cytochrome c oxidase subunits I, II, and III genes detected in Alzheimer's disease using single-strand conformation polymorphism.

A "mitochondrial hypothesis" of late onset Alzheimer's disease (AD) has been proposed. Biochemical studies indicate that there is a significant decrease in cytochrome oxidase (CO) activity as well as perturbed CO I and CO III mRNA levels in platelets and brain tissue from Alzheimer's patients. Using the electrophoretic mutation detection technique SSCP and DNA sequencing, we have identified 20 point mutations in the mitochondrial-encoded CO subunits (CO I, II, and III) in AD and age-matched control brain samples.