Mitochondrial disease: How mitochondrial disoder is related to neurological disease Part 2

Welcome back guys!!! Let continue at where we stop in the last post!!

RECAP:
-To transmit neurotransmitter, the synaptic vesicles need to be broken down. Calcium ions Ca2+ is able to bind to the synaptic vesicles and cause the synaptic vesicles to be broken down.

-During the process of transmitting neurotransmitter, the synaptic neurons will take in calcium ions through the voltage-dependent calcium(Ca²⁺) channel. Neurons also have receptors such as glutamate receptors and NMDA receptors to further increase the permeability of Ca2+ ions into the cell.

-The whole process cause an increase in Ca2+ concentration in the cytosol of the cells. High amount of Ca2+ ions in the cell will activate a cascade of event that initiate cell death.

-Mitochondria have the ability to intake large amount of Ca2+ ions and store it. Hence, mitochondria play a major role in regulating Ca2+ concentration in the cytosol of cell.


After the Recap, let continue where we stop last week.
  ARE YOU READY?? LET BEGIN

Mutation in mitochondria will cause a defects in the ETC. In addition, defects in mitochondria will inevitably affects the ionic balance for ions like Ca2+ and Na+ in neurons, causing transmission of electrical signals to be ineffective. When cells like neurons is unable to remove Ca2+ in the cytosol efficiently, cell death will occur. Many Recent studies show ill-functioned Mitochondria are involved in causing neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis(ALS). This is because the structure or function of the mitochondria in those cells linked to these diseases are altered.  With these studies, suggested therapies of neurological diseases could include anti-oxidants or agents that regulate mitochondrial and cytosolic Ca2+ concentration.

These findings over the recent years have shown mitochondrial disorder play a part in neurological diseases. However, many pathways of the mitochondria is still remain unknown. Hence, it still to early for scientists to conclude that mitochondrial disorder directly cause neurological diseases. More research and studies have to be done to obtain a more accurate data on how mitochondrial disorder can cause neurological diseases. Scientists believe that in the near future, cures for mitochondrial disorder and neurodegenerative diseases will be discovered

Alright guys!!! Thank you for reading our blog. But before I end, I believe that some of you are curious why are we doing research on mitochondrial diseases, am I right??

http://www.mitoaction.org/blog/categories/our-stories

Have a look at the website that I post above. They are stories about patients with mitochondrial disorder. After reading these stories, we realised is important we raise awareness on mitochondrial disorder as many people don't even know these of of diseases occur in our world. I will end my sharing here today!! Feel free to put in any comments. Thank you!!!

Mitochondrial disease: How mitochondrial disoder is related to neurological disease Part 1

Welcome back guys!! Thank you for coming back!!!

From the previous post, we learn a bit on mitochondrial diseases and what cause mitochondrial disease. But have you guys notice something interesting?? Yes!! All mitochondrial disorders seem to be related neurological diseases. So today and the next post, I will be sharing more on how mitochondrial diseases can play a part in causing neurological diseases. At the same, I will be using a scientific paper to show the relationship between mitochondrial diseases and neurological diseases.

To discuss about neurological diseases, we need to know a little more on the nervous system.

Nervous system:
Firstly, we must know that the nervous system is make up of mainly two parts, Central Nervous System(CNS) and Peripheral Nervous System(PNS). In addition,we must know that the main function of nervous system is to transmit electrical pulses around the body. Lastly, to transmit electrical signal, neurotransmitter is used. Neurotransmitters are endogenous chemicals help to transmit signals across a synapse cleft from one neuron to another neuron. Look at the video below to help you understand more about the nervous system if you are unsure.

youtube: https://www.youtube.com/watch?v=4M82WwFACLg

Alright!! Now you have some basic knowledge on the nervous system. So now let focus more on how Calcium ions play an important in transmitting neurotransmitter across the synaptic cleft. .
http://en.wikipedia.org/wiki/Neurotransmission


To transmit neurotransmitter across the synaptic cleft, neurotransmitter in the synaptic vesicles need to be broken down and release the neurotransmitter.

Ca2+ ions plays an important role in breaking down the synaptic vesicle. During electrical transmission, voltage-dependent calcium(Ca²⁺) channels on presynaptic membrane open to allows Ca²⁺ ions to enter into the neurons. In addition, neurons have receptors such as glutamate receptors and NMDA receptors to further increase the permeability of Ca2+ ions into the cell. Synaptic vesicles in the neurons are broken when the Ca²⁺ ions binds to the vesicle membrane. This breakage causes the release of neurotransmitters inside the vesicle to be released into the synaptic cleft.


However, high concentration of Ca2+ ions in the cytosol will activate a cascade of event that will eventually cause cell death. To prevent this problem, mitochondria will be used to regulate the Ca2+ ions concentraion. The mitochondrion thus serves as a high capacity, relatively low affinity buffering system in regulating Ca2+ concentration.

 

Today I will be stopping here. In the next post, I will be continuing the topic on how mitochondrial disorder can cause neurological disease.


References:
http://www.macalester.edu/academics/psychology/whathap/ubnrp/meth08/biochemistry/neurotransmission.html
http://en.wikipedia.org/wiki/Neurotransmission
http://www.mind.ilstu.edu/curriculum/neurons_intro/neurons_intro.php

Research paper:Mitochondria, Ca2+ and neurodegenerative disease (www.elsevier.com/locate/ejphar)

Mitochondrial Disease

Hello guys, Welcome back!! From all the previous posts, I have been sharing a lot on what is Mitochondria and what crucial roles does Mitochondria play in cells. So today I will be sharing with you more about Mitochondrial diseases. Before I start, have a guess what causes Mitochondrial diseases and will happen when Mitochondria become dysfunction??

kenickbiochems12.wikispaces.com

What causes Mitochondrial disease or Mitochondrial disorder??
The answer is very simple. Mitochondrial diseases or disorder are cause by mutations in the Mitochondria DNA. From the previous post, we learned that Mitochondria DNA contains the genetic sequence that code for all the proteins require for the mitochondria to work properly. When a mutation occur, the amino acid synthesized may be different, thus, changing the 3D shape of the proteins needed for the mitochondria to function efficiently. Since mitochondrial diseases are cause by mutation in the Mitochondria DNA, different mutation at different genes will cause different disorders. Hence, there are many types of mitochondrial diseases.

Here are some mitochondria diseases: 
-NADH dehydrogenase (NADH-CoQ reductase) deficiency
-Leigh Syndrome
 -Alpers Huttenlocher syndrome
   
NADH Dehydrogenase (NADH-CoQ reductase) Deficiency:
NADH dehydrogenase deficiency is also known as Complex I deficiency. It is the most common site for mitochondrial abnormalities. Since Complex I is located at the Electron Transport Chain(ETC), when mutation occur, the process of oxidation phosphorylation will be greatly affected. Hence, the amount of ATP the cells is able to synthesize is very low.

NADH Dehydrogenase Deficiency cause a variety of clinical symptoms, especially for the organs and tissue that require large amount of ATP. Some examples are the brain, liver and muscles. In Additional, this disorder also cause progressive neurodegenerative disorders.

There are three major forms of this disease: Myopathy (muscle disease), Mitochondrial encephalomyopathy (brain and muscle disease), Fatal infantile multisystem disorder 

Myopathy: Symptom can start occuring in childhood and adulthood. Symptoms include weak body and exercise intolerance.
Mitochondrial Encephalomyopathy: Symptom can start occuring in childhood and adulthood. Symptoms include eye muscle paralysis, sensory neuropathy (nerve damage involving the sense organs), seizures and ataxia (abnormal muscle coordination). Can lead to cause Leigh Syndrome.
Fatal infantile multisystem disorder: Symptoms include poor muscle development, developmental delay, heart disease and respiratory failure.


Leigh Syndrome:
Leigh Syndrome is a severe neurodegeneative disease that occur during the first year of life. This disease cause progressive loss of mental and movement abilities which results in death within a couple of years due to respiratory failure.
Some clinical symptoms frequent vomiting, diarrhea, and difficulty swallowing infants. Hence, affected patients have inability to to grow normally. In addition, Severe muscle and movement problems are common in Leigh syndrome.
www.youtube.com


Alpers Huttenlocher Syndrome:
Alpers-Huttenlocher syndrome is a disease cause by mutations in the POLG gene. This disease has a range of similar symptoms involving muscle tissues and brain tissue. Symptoms of Alpers-Huttenlocher syndrome usually appear in children between age from 2 to 4. Symptoms include recurrent seizures, brain related problems and uncontrollable muscle coordination.

Treatment and Therapies
Can Mitochondrial disease be cure??
Currently, there is no cure for mitochondria disease. Treatments and Therapies can only help to alleviate and slow down the progression of these diseases. As there are many different type of mitochondrial diseases, treatments and Therapies varies from patient to patient, depending on the exact disorder that occur in the patient.

Okay, today I will be stopping here. If you have any questions or want to know more about the diseases that are mention above, feel free to put your comment below. Bye!! Happy new year to you guys

References:
http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934635
http://ghr.nlm.nih.gov/condition/leigh-syndrome
http://ghr.nlm.nih.gov/condition/alpers-huttenlocher-syndrome
http://www.umdf.org/site/pp.aspx?c=8qKOJ0MvF7LUG&b=7934629
 

MItochondria: History of Mitochondria and DNA of Mitochondria

Hi guys!!! Today I will be sharing a bit on  History of Mitochondria and how is the DNA of Mitochondria differ from our DNA.

http://www.reddit.com/r/SketchDaily/comments/16vsl2/january_19th_biker_babes/

So are you ready to hear the story?? Let begin

Mitochondria story:
Once upon a time, about 2 billions years ago, when the earth is still developing, life on earth is still very simple. Organisms is believed to generate energy through a process known as fermentation. One day, an unique organism is born. This organism is unique because instead of generating energy through fermentation, it generate energy through a process called photosynthesis. Photosynthesis is the process where the organism convert light energy into chemical energy. The raw product for this process is carbon dioxide and the product produce is oxygen. This cause the the oxygen level to rise on earth and organisms that could not tolerate oxygen start to die.

Around that time, a family of bacteria called α-proteobacteria is born. One example for this group of organism is called Rickettsia prowazekii. Rickettsia prowazekii is able to use the oxygen present on earth to generate energy and reproduce, and the population begin to increase. However, Rickettsia prowazekii is a very small size bacterium, which are being eaten by other larger organism that is presented at that time.

As earth continue to change and 'mature',the earth atmosphere is constantly changing and organisms need to change in order to adapt and survive. At some point of time, Rickettsia prowazekii did not get broken down by the host organisms. Why? The reason might be because Rickettsia prowazekii has found a way to generate energy using oxygen for the host organisms. Since Rickettsia prowazekii is taken up by the host organisms, the host organisms protect Rickettsia prowazekii from other predatory organisms. This mutually beneficial relationship last for billions of years.

Billions of years passed by and Rickettsia prowazekii lost it independent functions. Rickettsia prowazekii is unable to survive as an independent organisms and become part of the host organisms known as Mitochondria. Mitochondria only retained some of it original DNA components which is necessary to produce energy using oxygen.


So how reliable is this story??
 
Here are some evidence to support this story:

1. Mitochondria have circular DNA which is similar to prokaryotes DNA but differ to the DNA on our chromosomes.
2. Mitochondria have two membranes. Similar to Prokaryotes.
3. Mitochondria's DNA is very similar to the DNA of Rickettsia prowazekii. However, Mitochondria have lesser DNA because some of the DNA is lost over the years.

http://www.quickmeme.com/meme/35p0em

DNA OF MITOCHONDRIA 

Before I begin talking about the Mitochondria DNA, let just relax and look at some pic of Mitochondria.

View under the electron microscope:
http://www.newcastle-mitochondria.com/mitochondria/what-do-mitochondria-do/

 The DNA of Mitochondria is found in the Matrix!! 

Interesting Fact: Mitochondria in cells are often not found in the 'bean shaped' structure. Instead, many mitochondrion join together to form beautiful branched networks that fill the cell. 
Here a pic how it look like:
 
These networks constantly change and reshape itself. The reason for this may be because when mitochondria form networks, it allow the contents in the matrix to mix.

Now let talk begin to talk more on Mitochondria DNA!!! 
 
Firstly, how is Mitochondria DNA is different from the DNA we found in our own nucleus???
1.Mitochondria DNA is circular while the DNA within our chromosomes has a double helix shape.
2.Mitochondria DNA contains only 16,500 base pairs compared to over 3 billion pairs in the nuclear DNA.
3. Each cell contains two copies of each double helix chromosome while each mitochondria contains many copies of the circular mitochondrial DNA.
4. The DNA found in our nucleus comes from both our parents. However, the mitochondrial DNA only come from the mother(Maternal inheritance). This mean that the children will only inherit their entire mitochondrial DNA from their mothers.

Now the question is why is Mitochondria DNA important???
Mitochondrial DNA contains all the important information that mitochondria need to make proteins that is able to generate energy. In total, Mitochondria DNA contains about 37 genes and all these genes are vital for making the mitochondria and hence our cells work properly. If there is any mutations in the Mitochondria DNA, the cells could not function properly and it will lead to mitochondria diseases.

Today I will be stopping here. Sorry for the long text!! Hahaha... Just like always, we hope you learn something and feel free to make any comments!!!
  BYE BYE!!!!!

References:
http://www.newcastle-mitochondria.com/mitochondria/what-do-mitochondria-do/
http://en.wikipedia.org/wiki/Mitochondrion