What Is Mitochondrial Dysfunction?

Duchenne Muscular Dystrophy is a sex-linked disease, which is inherited in a recessive fashion (National Human Genome Research Institute, 2013). Over thirty similar genetic disorders exist (Duchenne Foundation Australia, 2015). All types of muscular dystrophy are considered to be a rare disorder (Duchenne Foundation Australia, 2015). Duchenne Muscular Dystrophy is most common in children and causes muscle weakness and wasting, which commonly begins in the lower limbs (Duchenne Foundation Australia, 2015; National Human Genome Research Institute, 2013). The disease itself is caused by changes to the DMD gene, which is responsible for providing instructions regarding the creation of the dystrophin protein in one’s muscles (Duchenne Foundation Australia, 2015). This protein is responsible for protecting muscles from damage, and without it the cells of a person’s muscles deteriorate and symptoms of Duchenne Muscular Dystrophy are exhibited (Duchenne Foundation Australia, 2015). The disease results from changes in the DMD gene, or other genetic changes in a child (Duchenne Foundation Australia, 2015).

Mitochondrial Neurogastrointestinal Encephalopathy disease (MNGIE) is an extremely rare disease that affects the process of muscles and shows up in equal numbers of men and women. Only 70 cases of this disease have been reported. A mutation of the thymidine phosphorylase causes MNGIE and lowers the production of adenosine triphosphate production.

Methods: 11 mild to moderate asthmatic subjects and 6 healthy normal controls underwent bronchoscopy with airway brushings to obtain airway epithelial cells. The cells were cultured at an air-liquid interface in varying concentrations of L-arginine and ADMA (100μM) and stimulated with IL-13 (10ng/ml) and INFɣ (both 10ng/ml) to determine the effects of ADMA and L-arginine, on markers of oxidative/nitrosative stress (NO-related metabolites (nitrites + nitrates or NOx), hydrogen peroxide and nitrotyrosine levels). A separate subset of obese late-onset asthmatic subjectss were randomized to receive 3gr/d of oral L-citrulline for 7 days to determine the effect of L-citrulline supplementation on plasma and sputum L-arginine and ADMA concentration in content.

(8). Our preliminary data indicate that alveolar type (ATII) cells isolated from individuals with emphysema have higher nuclear DSBs than control smokers or nonsmokers. Moreover, we observed an increase in mtDNA damage in ATII cells in this disease in comparison with controls. We also found lower XRCC4-like factor (XLF) expression, which is involved in NHEJ pathway (9, 10), in ATII cells in emphysema in comparison with controls. Furthermore, we detected that high oxidative stress induced by exposure to cigarette smoke induces XLF oxidation and localization in mitochondria. DJ-1 is a cytoprotective protein localized in mitochondria. However, we observed that it interacts with XLF in ATII cells in emphysema, which indicates the critical role of XLF/DJ-1 complex in mitochondrial function. In addition, our results suggest that the number of mitochondria is decreased in these cells isolated from emphysema patients in comparison with control smokers and nonsmokers. Our hypothesis is that high levels of ROS in emphysema induce XLF oxidation and mtDNA damage leading to mitophagy and cell death (Fig. 1). Elucidating the molecular mechanisms contributing to mitophagy in primary ATII cells will advance our understanding of the contribution of mitochondria physiology to emphysema development. ATII cells will be isolated from excess tissue obtained from lung transplants of patients with emphysema, Veterans with respiratory problems and from control organ donors

Asthma and COPD (chronic obstructive pulmonary disease) are the most common inflammatory diseases of the lung. Asthma is an inflammatory disease of the respiratory tract and characterized by bronchial hyper-reactivity, airway constriction, loss of breath, wheezing and mucus production in the lung. In the world, the number of individuals suffering from asthma is increasing at an alarming rate. About 18.7 million adults and 6.8 million of children in the United States suffer from asthma as reported by CDC (Asthma, n.d.). Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease that leads to obstructed airflow from the lungs. Inflammatory response to cigarette smoke is a major cause for the development of chronic obstructive

Asthma is capable of affecting the respiratory system directly as the Asthma causes a spasm and tightening of the bronchial passage and the swelling and the aggravation of their mucous lining, the body’s reaction also may cause harm as is triggers the defense cells in the immune system which consequently causes the airways to swell and the muscles surrounding the airways to contract.

Presbycusis or Age-related hearing impairment is the most frequent sensory disorder in the adults. It affects more than half of all adults by age seventy-five years. Presbycusis is an irreversible symmetrical progressive loss of hearing sensitivity during the lifespan. It has an insidious onset without clinical manifestation so detected by the routine diagnostic test after losing or damaging to inner ear cells and neurons. Presbycusis counted as an untreatable disorder since these inner ear structures lose the ability of regeneration. Mitochondria by production reactive oxygen species or inducing apoptotic genes is one of most prominent intracellular organelles that contribute in presbycusis progression. The present study focused on mitochondrial

Asthma, a chronic respiratory disease, affects countless people around the globe each and every year (WHO, 2014, para. 1-2). Although this respiratory disease can affect people of all ages, it is most prominent during the childhood years (Adams et al, 2014, p.587). Specifically, as defined by the text, Pharmacology for Nurses: A Pathophysiologic Approach asthma is defined as, “a chronic pulmonary disease with inflammatory and bronchospasm components” (Adams et al, 2014, p. 586). This inflammation and tightening of the airways makes it very difficult for a person with asthma to fill their lungs with air and thus they have great difficulty when trying to breathe (WHO, 2014, para 1-2). Furthermore,

According to the United Mitochondrial Disease Foundation (UMDF), between 1000 and 4000 children in the United States are born with the disease annually. The disease results from the failure of mitochondria, which are specialized structures in the blood stream that functions to process oxygen and convert nutrients to energy that the body can utilize to sustain life and support growth. Mitochondrial disease is a chronic genetic disorder and there are many forms of the disease, with varying symptoms that tends to affects each sufferer differently. The handful of studies that evaluate the direct effect that marijuana has on mitochondrial disease, largely focuses on its efficacy

VPS35 is a gene that plays a huge role in the membrane protein-recycling retromer complex. There are three genes that are known to be associated with Parkinson’s disease, SNCA and LRRK2, which are similar to each other, and one that is different. VPS35 is the third gene associated with Parkinson’s disease that causes an increase in the degrading of DML 1 complexes. The authors of this article want to know why mutation of the VPS35 gene leads to neurodegeneration. The researchers used mice for their experiment that housed the VPS35 mutant gene.

Mitochondrial reactive oxygen species (mROS) can have two effects on the mitochondria when produced in excess. It can result in the activation of protective pathways in the mitochondria as well as activate the opening of the mitochondrial permeability transition pore (mPTP). The mPTP core is speculated to have come from the ATP synthase dimer and can arrange into a nonselective channel. The opening function of the mPTP is normal within the mitochondria, but long and frequent opening of the pore is predicted to increase aging and the chance of developing degenerative diseases. mROS is further produced when the mPTP opens for long periods of time as well as the release of calcium, NAD+, and glutathione. Excessive release of these metabolites

To investigate the effects of SS-31 on the mitochondria in cells derived from FRDA patients, we detected MMP with the lipophilic dye JC-1 by measuring a potential-dependent shift in fluorescence from green to red, which reflected its aggregation in mitochondria29. The increased ratio of red versus green fluorescence in patient-derived cells after SS-31 treatment indicated more polarised mitochondria (Fig. 2a). Intracellular ATP level is another pivotal measure of mitochondrial quality. We found that SS-31 treatment significantly raised ATP levels in patient-derived cells (Fig. 2b), indicating increased oxidative phosphorylation. The ratio of NADH/NAD+ in patient-derived lymphoblasts was also measured and was found to be significantly reduced to the levels comparable to the healthy control cells (Fig. 2c). These results indicate much improvement of mitochondrial quality in patient-derived lymphoblasts post SS-31 treatment. Furthermore, we quantified the copy number of mitochondrial DNA and found that SS-31 treatment mildly increased the copy number of mitochondria in patient-derived lymphoblasts (Fig. 2d). Electron microscopic data substantiated these results revealing structural improvements from abnormal cristae in patient-derived cells to regular invagination of the inner membrane after SS-31 treatment (Fig. 2e). Taken together, SS-31 improved the

Mitochondria play a key role in the apoptotic process, being involved in two distinct signaling pathways: (1) maintenance of ATP production, and (2) mitochondrial membrane potential and mitochondrial membrane permeability. The mitochondrial membrane potential results from the difference in the electrical potential generated by the electrochemical gradient across the inner membrane, which is critical for maintaining the physiological function of the respiratory chain to generate ATP. Therefore, changes in the ∆Ψm have been originally proposed to be early and obligate events in the apoptotic signaling pathway.

Asthma might be classified as acute, sub-acute or chronic inflammation of the airway. In asthma, there is a spastic contraction of the smooth muscle in the bronchioles[gyton]. The presence of this airway obstruction causes edema and mucus secretion. When there is an increased sensitivity to irritating stimuli, bronchoconstriction occurs leading to hyperplasia of smooth muscle, hyper secretion and dis-modeling of the epithelium.

Release of chemotactic and toxic mediators causes activation of macrophage and degranulation of mast cells, which can lead to an inflammatory response that is at the highest level in airway remodeling.5 It brings about subepithelial thickening, and changes of mucous glands and smooth muscles structure.5,12 In addition, there is some evidence in bronchial biopsies of the cases with acute-onset of IIA, including epithelial desquamation (denuded epithelium), significant detected number of lymphocytes (mononuclear inflammation), airway remodeling, collagen deposition in the bronchial wall (edematous mucosa).5,15,70 These types of alterations have been reported in the experiments with animal models as well.71 Furthermore, studies revealed that there are other alterations in this type of asthma, such as mucosal squamous cell metaplasia, basement membrane