Dysbindin-1 Case Study

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

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.

Mutations of two genes, Parkin and PINK1, have been identified in autosomal recessive Parkinsonism (Pickrell and Youle, 2015). The functions of PINK1 and Parkin have been implicated in the maintenance of healthy mitochondria through regulating mitochondrial dynamics and autophagy that eliminate dysfunctional mitochondria (Moran et al., 2012). Recently, the DJ-1 protein known by its antioxidant and transcriptional modulator function has been indicated to work with PINKs and Parkin to control mitochondrial function (Irrcher et al.,

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 PARK7 gene provides instructions for making the DJ-1 protein. This protein is found in many tissues and organs, including the brain. Studies indicate that the DJ-1 protein has several functions, however it is not fully understood how generic changes cause Parkinson’s disease or even understand it’s risks. One of the protein's functions may be to protect cells, particularly brain cells, from oxidative stress. Oxidative stress reflects an imbalance between the generation reactive oxygen species and a biological system’s ability to readily detoxify the reactive species. It occurs when unstable molecules called free radicals accumulate at levels that can damage or kill cells. Many radicals are unstable and highly reactive. They can neither donate or accept an electron. Additionally the DJ-1 protein may assist in delivering selected proteins to proteasomes, which are structures within cells that break down unneeded

On the other hand fusion is associated with optimization of mitochondrial functions and is regulated by three major proteins i.e. mitofusin 1(Mfn1), mitofusin 2(Mfn2) and optic atrophy protein1(OPA1). Mfn1 and Mfn2 are mitochondrial transmembrane proteins localized to the outer membrane. During mitochondrial fusion Mfn 1 and Mfn 2 form hetero-oligomeric and homo-oligomeric complexes that join outer membranes of mitochondria. Inner mitochondrial membrane fusion is mediated by OPA1 and Mfn 1. Mounting evidence implicate that the expression level of mitochondrial dynamin proteins i.e. Drp 1, Opa 1, Mfn-1, Mfn-2 is decreased in the pathogenesis of complex neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease while Fis-1 levels are increased which results in abnormal mitochondrial distribution in neurons of AD patients as compared to age-matched controls. These changes in mitochondrial dynamics significantly impact almost all aspects of mitochondrial functions including energy metabolism, calcium buffering, reactive oxygen species(ROS) generation and apoptosis

Until recent years, the mitochondrial genome, located in the mitochondrion, and the genetic information encoded by it have been given little attention. However, recently it became apparent that the mitochondrial genome, despite its small size, is crucial for the study of human evolution and disease, as mtDNA mutations lead to some serious diseases.

In vertebrates, Drp1 is recruited to the fission sites by a few proteins including Mff; experiments by Otera et al. showed that knockout of Mff reduced mitochondrial division due to decreased Drp1 recruitment [5]. Subsequent experiments revealed that ER-mitochondria contact sites might be related to mitochondrial division. Rowland et al. showed that the contact sites co-localized significantly with both Drp1 and Mff [1]. Friedman et al. used fluorescent live imaging to study ER and mitochondria dynamics and found that 87% of division events were “spatially linked” to the contact sites [6]. Although ER-mitochondria contacts and fission appear to be interrelated, they are independently regulated. Friedman et al. demonstrated that contact sites remained intact in Drp1 and Mff knockouts [6]. In addition, the contacts were intact after mitochondrial division was complete

Many physiological processes in the cells require the participation of both intra- and extra-mitochondrial enzyme reactions. A link between mitochondria and cytosol is provided by a group of proteins known as the mitochondrial carriers (MCs) family (Arco & Satrustegui, 2005; F. Palmieri, 2004). MCs comprise a family of about 40-50 proteins, depending on the organism, and provide the main communication between mitochondrial matrix and extra-mitochondrial spaces by transporting a wide range of metabolites, nucleotides and cofactors.

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

Mitochondria has many key molecules that are present within the organelle. Some of these molecules include oxaloacetate and succinate dehydrogenase, both in which play important roles in cellular respiration. Both of these substrates are essential for the Krebs Cycle, as they both produce ATP within the cycle (Wojtczak, Lech & Wojtczak, A.B. & Ernster, L. 1969). The shape and structure of the molecule oxaloacetate is similar to the components of the molecule succinate dehydrogenase. An active site is part of an enzyme in which a protein or substrate binds to an enzyme (“Active Site.”). Normally,

Mitochondria are important intracellular organelles responsible for life & death. The mitochondrial matrix has multiple copies of mitochondrial DNA whose replication are not related to the cell cycle. Thus replication of mitochondrial DNA occurs several times and leads to mutations due to error in replication. This leads to mitochondrial dysfunctions which subsequently leads to oxidative stress and an increase in ROS . The main function of mitochondria is to produce ATP by oxidative phosphorylation. It regulates a variety of metabolic and signaling pathways and also plays an important role in programmed cell death. Recent studies using animal models have shown the decline in mitochondrial function with age thus bringing out a relationship between mitochondrial dysfunction and

Researchers say, ultimately, mitochondrial therapy could be developed to help treat neurodegenerative diseases, which are characterized by dysfunctional energy production.

Mitochondria are crucial for cells, supplying up to 90% of the energy requirements for cellular function. Their correct localisation is crucial and ensured by a transport system. Mitochondrial trafficking in neurons is particularly critical, because mitochondria must leave the soma and travel along the axon and dendritic network to facilitate neuronal function. Abnormal mitochondrial trafficking has been reported in several neurological disorders, therefore the ability to quantify and analyse mitochondrial trafficking is vital to improving our understanding of their pathogenesis. Commercial software currently lacks an automated approach for performing such quantitation. Here, we demonstrate the development of the Mitochondrial Trafficking and

Mitochondrial morphology is found to be closely associated with apoptosis. It can be found linked to mitochondrial fragmentation which is concurrent with cytochrome c release during early stages of apoptosis facillated by Drp1 recruitment to mitochondria(4). It has been shown that RNAi knockdown of fission proteins Fis1 as well Drp1 will not only prevent fragmentation of mitochondria but also prevents cell from triggering apoptosis by inhibiting cytochrome c release. Similarly, fusion protein OPA1 overexpression will prevent cytochrome c release, this achieved by maintaining tight mitochondrial cristae junctions which inhibit the release of cytochrome c from mitochondrial intermembrane