Mitochondrial Dysfunction Research Paper

In the United Kingdom alone, 150 new born children per year suffer from life threatening, mitochondrial diseases. These diseases vary in severity from person to person, making them difficult to diagnose, and they inflict an array of ailments such as neurological problems, muscle weakness, visual or auditory impairments, heart, liver, and kidney disease,

A. SIGNIFICANCE. Our goal is to screen chemical libraries to identify compounds that modulate mitochondrial transport in hippocampal and cortical neurons. This study is significant in four ways: (1) There is an urgent need to develop CNS (Central Nervous System) active drugs. CNS disorders are not only staggeringly complex but are poorly treated diseases (Palmer and Stephenson, 2005). In the United States alone the annual cost for stroke, depression, Schizophrenia and Alzheimer’s disease are currently estimated to be over $250 billion annually (Pangalos et al., 2007). Despite the advances in translational medicine and pharmaceutical research little progress has been made in developing CNS therapeutics. Improving CNS drug discovery efforts is an urgent goal as an estimated 1.5 billion people suffer from CNS-related diseases worldwide. Unfortunately only a handful of new drugs have been brought to the market with very few in the pharmaceutical pipeline (Kissinger, 2011; Schoepp, 2011; Abbot, 2011). The majority of pharmaceutical companies have recently announced a shift from supporting internal drug discovery efforts in favor of academic and government partnerships (Schoepp, 2011). At Scripps Florida we have close interaction of state of the art high throughput small molecule screening and cutting-edge neuroscience research. Thus we are in a unique position to address the challenges in developing CNS therapeutics. (2) Mitochondrial dysfunction is part of the pathophysiology of

Mitochondria are often referred to as the powerhouses of the cells. They generate the energy that our cells need to do their jobs. For example, brain cells need a lot of energy to be able to communicate with each other and also to communicate with parts of the body that may be far away, to do this substances need to be transported along the cells, which needs lots of energy. Muscle fibres also need a lot of energy to help us to move, maintain our posture and lift objects.

Once a upon time, there was a lonely mitochondria named Sophia Mitochondria. Sophia Mitochondria had been alone for a while and she does not know where her parents are. She want to find her parents so she decided to talk someone to help her which is her childhood best friend, David Chloroplast. However, before she called him, she did her normal routine. She took nutrients from one of their cells, breaks it down and turn it into energy. This routine is also known as cellular respiration. After that, she call her David Chloroplast and thirty minutes later, David Chloroplast was in front of her house. David Chloroplast and Sophia Mitochondria came to Bacteria Garden which Sophia Mitochondria’s parents favorite place to go every weekend. When they

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 shape of the mitochondria perfectly allows it to produce at their best. They are made of two membranes. The membrane on the inside folds over many times and creates cristae, a layered structure. The membrane on the outside acts like skin, and covers the organelle. Inside the mitochondria, there is a contained liquid called matrix. In the matrix we can find ribosomes and floating DNA. We can also find here granules, which are structures which may control concentrations of ions. The surface area inside the organelle increases due to the folding of the inner membrane. Many of the chemical reactions that occur in the mitochondria take place in the inner membrane, so this increased surface area gives more space for the chemical reactions to occur. It´s like this, you can get more work done if you have more space to do the work. We can observe similar strategies involving surface area in the microvilli in our intestines.

Human eyes are highly dependent on mitochondria for energy, thus are commonly affected by mitochondrial defects. For instance, people with Kearns-Sayre syndrome have a single, large deletion of mitochondrial DNA. The deletions range from 1,000 to 10,000 nucleotides, and the most common deletion is 4,997 nucleotides (9). The mitochondrial DNA deletions result in the loss of genes that produce proteins required for oxidative phosphorylation, causing a decrease in cellular energy production

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.

The cell’s mitochondrial population is normally highly dynamic and exhibits variable turnover rates. The turnover process is accomplished by an actively regulated transcriptional network for mitochondrial replenishment that is coordinated with the degradation and elimination of senescent and damaged mitochondria by selective mitochondrial autophagy or mitophagy. Although mitochondria are constantly renewed, the ongoing rate of homeostatic QC processes in vivo is fairly low (Miwa et al., 2008) on the order of days, whereas in cells, it is more rapid (Hernandez et al., 2013). Mitochondrial turnover in the rat heart has an estimated half-life of roughly two weeks (Rabinowitz and Zak, 1975). Thus, for a typical cardiomyocyte under basal conditions (~1000 mitochondria), 1.5 mitochondria would be replaced each hour. Moreover, mitochondrial turnover may be regulated by the circadian clock as a number of OXPHOS enzymes show strong diurnal variation in expression. This may be related in part to the period of fasting during sleep; therefore mitochondrial turnover at night may be more active with a few percent of the mitochondrial population replaced each night. Mitochondrial turnover rates also vary with specific metabolic status of tissues, but can be greatly

In pancreas cells, the mtDNA depletion can contribute to the age-related decline in insulin secretory capacity in man [55]. Also, the immunoreactivities of many mitochondrial enzymes, such as cytochrome oxidase, an important enzyme located on the inner mitochondrial membrane and a component of aerobic metabolism, respiratory chain and ATP synthetase complex, decrease when the age-related mitochondrial bioenergetics happens [42]. The extent of decrease or loss of this enzyme represents the loss of bioenergetic capacity [48]. As it was mentioned before, these age-related mitochondrial defects can all be detected by histochemical staining of MTCO1, which is an important biomarkers of mitochondrial function. Besides, the oxidative damage can trigger the release of intermembrane space proteins, such as cytochrome c (cyt c) into the cytosol and opening of the permeability of transition pore, causing a cascade of cell apoptosis [53,

Mitochondria is one of the main organelles inside a cell. It is considered the energy factory and has many functions all over the cell. Its main purpose is to make ATP, or adenosine triphosphate. ATP is the energy that every cell in the body can use to stay alive and continue each individual function. “Mitochondrion is a combination of the Greek words mitos (thread) and chondros (granule)” (van der Giezen). “Mitochondria are eukaryotic, membrane-enclosed, 1-10um sized organelles, described as ‘cellular power plants’ as they are responsible for the production of adenosine triphosphate (ATP) and oxidative phosphorylation” (Mulchandani). The Mitochondria interacts with other places in the cell by giving them energy to perform their functions.

Factors which have a detrimental effect on mitochondrial function include nutrient deficiencies, toxic metal/toxic chemical exposures, infections with certain viruses, and even poor diets. The mitochondria are the powerhouses of the cell. They make ATP and provide energy for our cells. In the process of producing ATP they create reactive oxygen species (ROS). These ROS cause oxidative damage to the mitochondria and other cells (Remmen & Richardson, 2011). When mitochondria become damaged through oxidative stress they produce less energy and actually increase the amount of ROS produced (Remmen & Richardson, 2011).

Mitochondrial DNA (mtDNA) are inherited from the mother and are prone to mutations (Pang & Ho, 2016). Mutations are not completely uncommon and is present in different cells currently, however, when the mutation percentage goes too high, it can lead to mitochondrial diseases. There’s an estimate that 1 in 5000 children are suffering from mtDNA mutation related diseases (Pang & Ho, 2016). Mitochondrial diseases help produce 90% of the energy needed for our body (United Mitochondrial Disease Foundation, 20017). When the mitochondria stop functioning properly, different organs start to fail as cell death starts to occur from lack of energy.

However, amplification efficiency of a short fragment is independent on mtDNA damage. We found higher mtDNA damage (Fig. 10A) and lower mitochondria amount (Fig. 10B) in emphysema in comparison with controls. We also wanted to analyze changes in mitochondrial amount in A549 cells treated with H2O2 for 0.5h, 1h, 1.5h and 2h. We used Tom20 as a marker of mitochondria and live cell confocal microscopy (Zeiss LSM 510). We found time-dependent decreased mitochondrial amount after 2h treatment (Fig. 11).

Mutations in egg or sperm cells are passed down to offspring. The damage to the other cells in the body is not passed down but is singular to that individual. Most cells will repair themselves and correct any mutations. However, over time, the damage which is not corrected accrues leading to the cells malfunctioning and dying. The Genome Maintenance or Somatic DNA damage Theory proposes that this accumulated damage speeds up the Ageing process. Evidence to support the theory was found in a number of different cells taken from elderly subjects. The blood and skin cells of elderly people were found to have a decline in their capacity to repair damage compared to that of younger subjects. A study looking at the white blood cells (responsible for immune response) also found that the DNA damage was approximately 2-4 percent in younger people while older people had almost six times this value. This result gave evidence to support both the Genome Maintenance Theory as well as the Immunological Theory of Ageing. Furthermore, a study into Werner’s Syndrome- a disease which causes accelerated ageing- showed that a mutation in the WRN gene lead to malfunctioning of DNA replication and repair of DNA damage. Cancer is also associated with the Ageing process and patients