Effects Of Mitochondrion On The Mitochondrial Oxphos Machinery System

OXPHOS begins with the entry of electrons into the respiratory chain through CI or CII (Succinate:ubiquinone oxidoreductase). NADH ubiquinone oxidoreductase (EC 1.6.5.3), also known as Complex I, is the first and the largest membrane-bound enzyme of the electron transport chain. It oxidizes NADH and transfers electrons through seven iron sulfur clusters to the membrane soluble ubiquinone, coenzyme Q. At the same time, for every pair of electron, it pumps four protons across the membrane, which contribute to the proton gradient necessary for ATP production by ATP synthase (complex V) [1]. Electrons can enter the chain directly through CII from succinate and be transferred to ubiquinone [3].

Under normal conditions, the mitochondria maintain cytosolic Ca2+ levels, which is necessary for normal cellular function. However, the mitochondrial uptake of excessive levels of Ca2+ can lead to inhibition of ATP synthesis, disruption of mitochondrial membrane potential, increased ROS production, and generation of the mitochondrial permeability transition (mPT) state, which is thought to occur in response to formation of the mPT pore. As a consequence, cellular demise can occur through necrotic-related mechanisms events, including a loss of energy production and oxidative stress as well as apoptotic-related mechanisms, including the mitochondrial release of pro-apoptotic proteins. Given the central role of the mitochondria in cell

The mitochondria has been known as the powerhouse of the cell. What does that even mean? Well, what it means that the mitochondria does all of the cell energy conversion. It takes nutrients from the cell and transforms it into viable ATP. ATP, molecule adenosine triphosphate, is the energy that cells can use. The process in turning nutrients into ATP is called ATP Synthase. The first part of ATP synthase is an ending of cellular respiration. The mitochondria plays a small but large role in the cell. The structure of the mitochondria plays a huge part of cellular respiration. Mitochondrial structure has two membranes an inner and an outer. Inside the inner membrane you have the matrix and the cristae. The first part of cellular respiration is glycolysis, it is made outside of the mitochondria in a gel like fluid called the cytoplasm. Next, is the citric acid cycle, also known as the Krebs cycle, named after the German researcher Hans Krebs, goes in through the outer membrane. Enzyme Acetyl CoA enters and combines the two carbon groups with another four carbon groups. The result is six carbon molecules citrate, which are acidic. The next part in the Krebs cycle is that the hydrogen atoms are stripped and produce NADH molecules. The final Krebs step is; ADP is transferred to ATP the succinate is oxidized forming another four carbon molecule. The two hydrogen carbons react and their electrons transform from FAD to FADH2. The Krebs cycle makes only about 4 ATP and in the

In a single cell there are large numbers of organelles known as mitochondria. These organelles are spherical with a double-membrane, the outer mitochondrial membrane and the inner mitochondrial membrane (Chial). The majority of energy and power for the body’s cells, more than 90% of what is required to preserve life and encourage growth, originates from these organelles in the form of the molecule adenosine triphosphate (Kurt 11; “What”). This energy production process is termed oxidative phosphorylation because it occurs in the presence of oxygen (Sirrs). If there is a fault in this assembling of energy within the mitochondria, it is known as a mitochondrial disease. Usually the organs affected by these diseases are those that require

It functions as a strong uncoupling agent on liver cell mitochondria, and further alter cell metabolism by uncoupling oxidative phosphorylation and glycolysis. More specifically, Tamoxifen inhibits the activities of complex II+III (IC50 =15µM) and complex V (IC50 =8.1µM) [6] of the electron transport chain. The IC50 doses of tamoxifen in liver cell mitochondria agree with reported cytotoxic doses in MCF10A and the observed cytotoxic doses in this study, which further supports that the potential mechanism governing tamoxifen toxicity is due to its inhibition of this pathway.

Assay of succinate dehydrogenase of after isolation of mitochondria in Cauliflower (Brassica oleracea) using differential centrifugation.

Mitochondria are a major source of cell superoxide generation that in turn yields a spectrum of secondary reactive species. They serve multiple functions, including regulation of intracellular calcium stores, ATP production, activation of caspases, and regulation of redox signaling. The outer mitochondrial membrane is porous and allows for passage of low molecular substances between the cytosol, the inter-mitochondrial compartment, and the matrix. Mitochondrial dysfunction is characterized by a decreased ATP production, decreased membrane potential, decreased expression of mitochondrial complexes I, III, IV and increased mitochondrial respiration and ROS production, has been observed in the inflamed airways of asthmatic subjects. Excessive

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

The mitochondrial pathway, also called intrinsic pathway, because it is initiated from inside the cell. Various stimuli such as growth factors withdrawal, DNA-damage, hypoxia, and oxidative stress can induce apoptosis through this cascade. These insults cause increasing permeability of the outer mitochondrial membrane and opening of the mitochondrial permeability transition (MPT) pore which is controlled by members of the Bcl-2 family proteins. This large family of proteins is defined by the presence of conserved Bcl-2 homology domains (BH1 to BH4). Up to 30 Bcl-2 family genes have been identified in mammals, which have either pro-apoptotic or anti-apoptotic functions. Some of the anti-apoptotic members include Bcl-2 itself, Bcl-XL, Bcl-w, BAG and Mcl-1 which possess all domains of BH1 to BH4. The pro-apoptotic family proteins can be divided into two subgroups: consists of Bak, Bax, and Bok with possess BH1 to BH3 domains, and Bad, Bid, Bik, BNIP3, Bim, Bmf, Blk, Hrk, Noxa, Puma, and Spike) that only possesses BH3 domain [Cory, 2002; Mund, 2003]. It is believe that BH3-only proteins interfere with the fine-tuned balance of homo- or hetero-oligomerization between pro-apoptotic multidomains (eg., Bax/Bak) and anti-apoptotic members (eg., Bcl-2/Bcl-XL) (Figure 3). In general, oligomers of Bak, Bax, and Bok induce PMT, either by forming channels by themselves or by interacting with components of the PMT [Antonsson, 2000]. Bad can also heterodimerize

Mitochondria are organelles found in the cytoplasm of eukaryotic cells and play a crucial role in the respiration of the cell (Bandelt et al, 2006). Mitochondria are thought to have originated as free-living bacteria that parasited proto-eukaryotic cells~1.5 billion years ago and have since remained in an endosymbiotic relationship inside eukaryotic cells (Margulis, 1981). The mitochondria preserve remnants of the original bacterial genome coding for key aspects of the mitochondrial machinery, but over the course of evolution, most mitochondrial genes have been transferred to the nucleus. The extent of these nuclear insertions was estimated to represent at least 400,000 base pairs (bp) in the human genome (Qu, Ma, & Li, 2008). The number of

Accumulation of DNA damage occurs with increasing age, causing cells to deteriorate and malfunction. While DNA damages incur constantly in cells of living organisms, most of the damages are repaired in healthy individuals. However, some DNA damage accumulate as the DNA polymerases and other repair mechanisms cannot correct defects at a rapid enough pace as the rate of damage. In particular, damage to mitochondrial DNA may lead to mitochondrial dysfunction. Maintenance of metabolic homeostasis along with appropriate stress responses absolutely requires proper mitochondrial function. Mitochondrial dysfunction is known to play a critical role in aging and as well as other numerous human diseases, for example cancer and neurodegenerative disorders

New reproductive techniques to prevent the inheritance of serious mitochondrial disease result in a child with three genetic parents. Their mtDNA comes from a donor female and their nuclear DNA from their biological mother and father. Is this a slippery slope towards a future of designer babies, where parents can choose the genetic attributes of their children?

The exposure of immune cells to whole pathogens or to various structurally diverse pathogen- and danger-associated molecular patterns (PAMPs and DAMPs) and environmental irritants triggers the assembly of multi-protein inflammasome complexes that are required for full expression of host inflammation. Inflammasomes generally contain a NOD-like receptor (NLR) sensor molecule, namely NLRP1 (NOD-, LRR- and pyrin domain-containing 1), NLRP3, or others (Latz et al., 2013). A typical complex consists of three protein components, for example NLRP3 (NALP3), ASC (PYCARD) and caspase-1. The NLRP3 complex activates caspase-1 (and caspase-11 in mice) leading to processing and release of IL1-B and IL-18.

In response to inflammatory stimulation, ROS may directly react with nuclear DNA, RNA, and lipids through oxidation, nitration and halogenation or activate the signaling pathways. Aerobic organisms are able to produce greater energy with the help of the mitochondrial respiratory chain as compared to anaerobic organisms. However, in aerobic respiration, electron is continuously leaked to O2 during mitochondrial ATP synthesis and hence gives rise to superoxide anion (O2-). Approximately 1–5% of total consumed oxygen in aerobic metabolism is converted into this ROS. The manganese-superoxide dismutase (Mn-SOD) is employed to degrade or dismutase superoxide anion into H2O2 and water and thus to protect the cell components from the harmful effect of this free radical (118).

Mitochondria are important organelle which is responsible for regulating cellular energy homeostasis and cell death. Hence, the damaged mitochondria could be removed by a mechanism called Mitophagy, which is has particular autophagic elimination mitochondrial (Youle and Narendra, 2011).as the mitochondria are targeted for autophagic degradation (Springer and Macleod, 2016). Furthermore, Mitophagy plays a significant role in cellular homeostasis by eliminating dysfunctional mitochondria and decreasing mitochondrial mass as a response stress. Recent work has linked defect in mitophagy to human diseases such as metabolic disorders diseases (Youle and Narendra, 2011). Furthermore, Metabolic myopathies are inherited or obtained defects in