Extra-Mitochondrial Family Structure

The genes which encode for the mitochondria’s component proteins are in 2 separate genetic systems in 2 different locations. One of which is the cell nucleus, but the other is inside the organelle itself. There are relatively few genes inside the

Electrons from CI or CII are then transferred through CoQ to CIII (cytochrome c reductase), then to cytochrome c, another electron carrier, and finally to complex IV (cytochrome c oxidase), where electrons are used to reduce O2 to H2O [4]. CI pumps protons out of the mitochondrial matrix with a stoichiometry of 4 protons to 2 electrons [2]. For every electron, the chain through complexes I, III and IV translocates a total of 5 protons from the mitochondrial matrix to the intermembrane space, creating a membrane potential that is used by the CV (ATP synthase) to generate ATP [5].

Mitochondria, dubbed the ‘powerhouse of the cell’, are a type of organelle present in most human cells. Their primary function is to generate Adenosine Triphosphate (ATP), the cell’s principal source of chemical energy. Unlike most other organelles, mitochondria store their own set of genetic material, distinct from the DNA situated in a cell’s nucleus. Although this ‘mitochondrial genome’ represents only 0.1% of a cell’s genetic information, it often plays a significant role in development.

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

(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

There are hundreds of neurodegenerative diseases (NDD) and the etiology for most of the random conditions remain a universal mystery (Nieoullon 2011). A deterioration of specific functions of the neuron cells of the central nervous system is the most common characteristic of NDD. Neurons are responsible for transmitting essential information to other nerve, muscle and glandular cells (Przedborksi, Jackson-Lewis 2003). Emerging research has recently identified mitochondrial dysfunction as a recurrent elemental link in numerous neurodegenerative disorders (Ghano,

The remaining 13 genes encode polypeptides which are synthesised in mitochondrial ribosomes. All of the 13 polypeptides are respiratory complex subunits, which are involved in oxidative phosphorylation, ensuring the production of adenosine triphosphate (ATP). The whole complex consists of approximately 100 polypeptides. Nuclear DNA encodes most of the polypeptides which are synthesised in the cytoplasm and then transported into the mitochondria.

The former are transmitted by maternal inheritance, while the latter have Mendelian inheritance. Most individuals with Leigh’s syndrome have an autosomal recessive or X-linked disorder of mitochondrial energy generation rather than an mtDNA mutation (Thorburn and Rahman 2003). Leigh’s syndrome arises mainly due to “dysfunction of the mitochondrial respiratory chain” (Chinnery 2000). An important cause of Leigh’s syndrome is “mutations in the complex IV assembly genes, particularly SURF1” (Lee et al. 2012). The SURF1 gene is found in nuclear DNA and is located on the long arm of chromosome 9. The gene defect in Leigh’s syndrome has been mapped to chromosome 9q34. SURF1 belongs to a family of genes called mitochondrial respiratory chain assembly factors and encodes a protein restricted to the inner membrane of the mitochondria. This SURF1 protein contains a unique mitochondrial targeting sequence at its N-terminus. The main function of SURF1 is to encode a factor involved in the biogenesis of the cytochrome c oxidase complex (Zhu et al.

carboxyl terminus is necessary to recruit mitochondria, and the N terminus is anchored to the

They found that the human mitochondrial heat shock protein 60 (mHsp60) and its cochaperonin, human mitochondrial heat shock protein

They provide the energy needed for the cell to carry out their functions. They have a double-layered membrane and have their very own DNA. Importantly, they are involved in immune response. These characteristics make them targets for pathogens.4 Contrary to what one might expect, the bacterial pathogens that target the mitochondria regulate the apoptotic properties of the organelle more so than their immune properties.4 They are able to alter the amount of survival and apoptosis of a cell and use that to their advantage.4 What makes this entire process possible is the bacterial MLS gene.5 These proteins interact with receptors on the mitochondrial membrane and once bound, they initate a signal cascade inside the organelle.5 MLS containing proteins can be found and are active in L.pneumophila. This bacterium does appear to use this strategy in certain situations, but more complete analysis is still required because the process is still

For example, each human mitochondrion contains about 10 identical molecules. The prokaryotic character of the organelle genome, suggests that mitochondria and chloroplasts are the relics of free living bacteria that formed a symbiotic association with the eukaryotic cell (endosymbiotic theory). MITOCHONDRIAL GENOME: MITOCHONDRIAL DNA : Each mitochondrion contains multiple mtDNA molecules. Thus the total amount of mtDNA in a cell depends on the number of mitochondria, the size of the mtDNA and the number molecules per mitochondrion. mtDNAs have been found to encode rRNAs, tRNAs and essential mitochondrial proteins.

After the unanticipated discovery of a separate mitochondrial genome, there have been new insights into its inheritance and mutation. There is enough evidence to bolster the fact that fusion between a-proteobacteria and archaebacteria is an integral event in evolution of eukaryotic cells. However, it has also been conjectured that eukaryotic cell may have originated from prokaryotes. As a part of this evolution, many mitochondrial ancestral genes were lost. These are the genes that were no longer required in their new host cell environment. All eukaryotes contain genes of mitochondrial origin in their nuclear genome. However, this is only true for a few genes. Studies indicate that humans and mice have only 35% of mitochondrial gene products that are similar to bacteria Rickettsia. Remaining mitochondrial proteins are derived from either non-mitochondrial nuclear genes or as a result of horizontal gene transfer events. Mitochondria have developed different states during the evolution of eukaryotic cell. Aerobic mitochondria retain a small mtDNA while anaerobic mitochondria and hydrogen-producing mitochondria alter the function of respiratory chain and also maintain mtDNA.

Mitochondria and chloroplasts have two membranes that surround them. The inner membrane is probably from the engulfed bacterium and this is supported by that the enzymes and proteins are most like their counterparts in prokaryotes. The outer membrane is formed from the plasma membrane or endoplasmic reticulum of the host cell. The electron transport enzymes and the H+ ATPase are only found in the mitochondria and chloroplasts of the eukaryotic cell. (2)

These sequences are sourced from Subunit 1 of the Cytochrome Oxidase gene in the Mitochondria.