Mitochondria Case Study

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

ALS, better known as Amyotrophic Lateral Sclerosis, is considered as a complex genetic disorder, in which multiple hereditary and environmental factors combine to cause this disease. This is seen as an illness of parts of the nervous system that control voluntary muscle movement. In ALS, the motor neurons (nerve cells that control muscle cells) are gradually lost. When these motor neurons turn out to be lost, the muscles they control become weak and ultimately nonfunctional. We see that “amyotrophic” is rooted in Greek origin meaning without nourishment to muscles and refers to the loss of signals nerve cells normally send to muscle cells. “Lateral” simply means to the side and refers to the location of the damage in the spinal cord. “Sclerosis” means hardened and refers to the toughened nature of the spinal cord in advanced ALS. This progressive neurodegenerative disease, that was first discovered 150 years ago, is associated with a life expectancy of approximately three years after symptom onset. In the United States, ALS is also known as Lou Gherig’s Disease, named after the Yankees Baseball player who passed away because of it in 1941. In the United Kingdom and other parts of the world, it’s often referred to as motor neuron disease in reference to the cells that are lost in the disorder (ALS Association, 2015).

Although it is not known how the SOD1 gene leads to ALS, there is increasing evidence that mutated SOD1 can become toxic. It was suggested that the changes in processing RNA molecules, the ones associated with gene regulation and activity, could be a factor to causing ALS, due to the discovery of certain genetic mutations, but it’s just a possibility. In 2011, there was a defect in the C9orf72 gene which was found in both ALS patients and some frontotemporal dementia patients, and suggests the genetic ties between both neurodegenerative disorders (Amyotrophic Lateral Sclerosis (ALS) Fact Sheet, 2016). Consequently, due to no concrete causes, there can be no definitive diagnosis. In order to detect ALS, a series of tests must be done, as it is diagnosed through the process of elimination. Some diagnostic testing includes an electromyography, which detects electrical activity in muscles. Magnetic resonance imaging (MRI) can also be done to show a detailed picture of the brain and spinal cord. A muscle and/or nerve sample from the body can be examined, as well as urine and blood

Mitochondrial dysfunction and oxidative stress have been consistently observed in brains of PD patients. There is increasing pharmacological and genetic evidence sustain a link between PD and mitochondrial respiratory chain dysfunction, particular a deficit in mitochondrial complex I (Franco-Iborra et al., 2015). Accidental exposure to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), an mitochondrial complex I inhibitor, has been known to result in acute and irreversible syndrome that was almost indistinguishable from PD (Calne and Langston, 1983; Langston and Ballard, 1983). Later on, mitochondrial complex I inhibition has been identified in the brains of sporadic PD patients (Schapira et al., 1990). In addition, chronic systemic inhibition of mitochondrial complex I by pesticide rotenone has been found to link to sporadic PD (Betarbet et al., 2000). Interestingly, mitochondrial complex I deficiency has been found not only in the postmortem substantia nigra but also in cerebral cortex (Schapira et al., 1990), which is consistent to the cortical glucose hypometabolism observed in PD patients. Indeed, the pathology of PD has been found to involve several brain regions other than the SNc and many neurotransmitters other than dopamine (Lang and Obeso, 2004a, b). PD models using MPTP and rotenone have now been used extensively in PD research (Beal,

Muscular dystrophy is a combination of diseases passed down through genes identified by progressive degeneration of the skeletal or voluntary muscles.(Alicia Foose,PhD, Patricia Ardovino,PhD,2008, p.141). This occurs due to mixture of hypertrophy, atrophy, and necrosis muscle cells. The muscle fibers increase in muscle size and results in muscle weakness while the muscle undergoes necrosis, fat and connective tissue replace the muscle fibers.(Sheila Grossman, Carol Mattson Porth,p.461).There are nine types of muscular dystrophy according to Alicia Foose, and Patricia Ardovino“Duchenne, Becker, Emery-Dreifuss, Limb-girdle, facioscapulohumeral, myotonic, oculopharyngeal distal, and congenital.”Each disease

In the 1970’s and 1980’s, neurologists further tested the waters for Duchenne muscular dystrophy, and its neurogenic theory. With the advent of DNA analysis in the past few decades there had finally been a clear distinction that could possibly be made with each individual who became a carrier of Duchenne muscular dystrophy, also referred to as DMD. During the later years of the nineteenth century and twentieth century there had been numerous attempts to identify and explain the origins and pathogenesis of muscular dystrophy but none were

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

In the research done by Deng et al 1993, they concluded that the loss of function was responsible by measuring the enzymatic activity of SOD1 mutants and found it to be on average which is less than half of wild-type SOD1. Since the original findings of linking SOD1 to ALS there now more than a hundred mutations that have been found on SOD1, most these mutations being missense mutations that affect the stability and folding of the enzyme (Beckman et al 2001). The aim of this research paper is to review recent researches and understand the role of oxidative stress that is associated with SOD1 mutations that can possibly lead to

There are several factors being explored as potential causes. Because there are familial cases of ALS, gene-related causes are worthy of investigation with the SOD1 (copper-zinc superoxide dismutase) gene being one of greater interest. Mutations in the SOD1 gene have been found in a fifth of familial cases of ALS (Rosen). Mutations to this gene, rather than having a detrimental effect on its own antioxidant enzyme function, appear to cause disease through toxic gain (Shaw). Oxidative stress and increase in reactive oxygen species can cause cell death, and because mutations in the SOD1 gene can allow this to occur, it could be a potential mechanism for ALS neural degeneration (Wijesk).

Spinal Muscular Atrophy (SMA) is defined as a genetic disease affecting the part of the nervous system that controls voluntary muscles. Atrophy means wasting away, hence exactly what the disease is doing. SMA is characterized by loss of motor neurons in the ventral horn of the spinal cord, leading to weakness and muscle atrophy (Monir Shababi, 2013). The motor nerves receive impulses that come from the brain to the spinal cord, and then transmit the impulses back to the muscles, so when the signals do not work, this is what causes SMA. The loss of these motor neurons leads to your muscles “wasting away.” These muscles are necessary in order for us to

Amyotrophic lateral sclerosis (ALS) is a late onset neurological disorder characterized by motor neuron degeneration in brain stem, spinal cord and primary motor cortex. There is no single gene strictly associated with all ALS cases, the disease is thought to be caused by the interaction of many genetic factors as well as environmental influences. Most of ALS patients have no family history of this disease, familiar form accounts for only 5 to 10% and seems to be dominant in most cases. The dominance and high heritability of familiar ALS (FALS) led to identification of several high-risk alleles of few genes (among those, SOD1, FUS, TARDEP, C9ORF72 are the most frequent)

Besides the appearance of episodic focal inflammatory lesions, there is a more generalized and progressive disease process that results in slow axonal , neuronal degeneration and subsequent accumulation of neurologic disabilities. The pathogenesis of this neurodegenerative process is aurged to the mitochondrial dysfunction which could be a key contributing mechanism ( Su et al., 2013)

Involvement of muscles in neurological disease has been extensively studied over the past century. By 1830, Charles Bell had identified muscular dystrophy as a cause of progressive weakness among boys (McConville & Vincent, 2002). After extensive research, it was established that the disorder was of neurological origin. Together with other diseases such as Myasthenia gravis, Parkinson disease among others, it has been determined that muscular involvement in these diseases arises from the neuromuscular connection. More importantly, many neural transmissions occur at the muscle junctions through the actions of neurotransmitters. Any changes in the amount or structural defects of the synapse cause muscular weakness and gradually loss of function. In other severe cases, loss of nerves at the junctions causes permanent disability since nerves cannot be regenerated. This focus will examine existing literature to provide an association of muscles properties and neurological involvement.

Mitochondrial damage is a normal part of aging, but is accelerated in many metabolic disorders. Chronic deficiencies and gut imbalances can destroys the mitochondrial membranes and lead to the modern diseases we see today.

In this study, the authors discovered a new gene mutation implicated in the onset of Leigh syndrome, a neurodegenerative disease caused by lesions in multiple parts of the central nervous system. The gene mutation was found in a girl with first-cousin parents. Since the girl did not contain mutations of the existing candidate genes for Leigh disease, whole-exome sequence was used to search for a novel homozygous mutation. It was discovered that the patient has a missense mutation in SLC25A46, a gene that codes for a mitochondrial metabolite carrier protein. The authors wanted to determine the role that mutant SLC25A46 has on causing Leigh syndrome. In addition, the authors wanted to make clear the molecular functions of wild-type SLC24A46.