BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Prokaryotic

Do Mitochondria contribute to neurological and psychiatric disorders?

Mitochondria have had a deep history through the evolution of eukaryotic cells. A primitive bacterium was engulfed by another free floating prokaryotic cell. Many think that this was originally how eukaryotic cells were formed and why mitochondria have their own DNA different from a their cells nucleus. Endosymbiotic theory has been used to understand the intricacies of Mitochondria and leaves many clues as to how their relationship with their cell affects its overall performance  The mutually beneficial relationship between both has lasted for over two billion years by fueling the processes for everyday life.

Mitochondria are membrane-bound cell organelles which generate majority of the chemical energy needed to power a cell’s biochemical reactions. Cell, Mitochondria, Biology, Organelle, ScientificChemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate or ATP. This is only one of the many essential jobs mitochondrion hold as an organelles in our cells.

Since mitochondria have their own set of DNA different from their cells, it makes it both a critical element of our cells and a potential source of problems. Mitochondrial DNA can harbor mutations similarly to ones in our nuclei. These can either be detrimental to their function powering our bodies or have little to no effect whatsoever. Age, stress and other factors may disrupt mitochondria’s many functions. On top of that, mitochondrial injury can release molecules that, due to their similarities to those made by bacteria, can be mistaken by our immune system as foreign invaders, triggering a harmful inflammatory response against our own cells.

One of our most important organs, the brain, needs mitochondria the most for its power driven functions. “The more energetically demanding a cell is, the more mitochondria they have, and the more critical that mitochondria health is — so there’s more potential for things to go wrong,” says Andrew Moehlman, postdoctoral researcher who studies neurodegeneration at the US National Institute of Neurological Disorders and Stroke (NINDS). Some estimates assume that each neuron can have up to two million mitochondria meanwhile there are eighty-six billion neurons in our brain.

Researchers have then linked dozens of disorders to alterations in mitochondrial DNA and nuclear DNA related to mitochondrial function. The majority of these are either neurological in nature or have some effect on the brain because of how dominant mitochondria is in the brain. According to Douglas Wallace, a doctoral student at Yale University, despite making up only 2 percent of a human’s body weight, the brain uses roughly a fifth of the body’s energy. These small reductions in mitochondrial function can have large effects on the brain, Wallace explains.

ATP gives us the energy we need for our body to function as we learned through our cellular respiration unit. Without this form of energy, our body simply cannot function which is why mitochondria play a key role in brain function. Mutations which affect the flow of ATP synthase seem most detrimental to cell function and as we know is where ADP and a Phosphorus join together to create ATP. Mitochondria’s own set of DNA makes it difficult to pinpoint a mutation and leaves animals vulnerable to neurological disorders.

New anti-CRISPR Proteins Serving as Impediments to this Miraculous System.

CRISPR-Cas9 systems are bacterial immune systems that specifically target genomic sequences that in turn can enable the bacterium to fight off infecting phages. CRISPR stands for “clusters of regularly interspaced short palindromic repeats” and was  first demonstrated experimentally by Rodolphe Barrangou and a team of researchers at Danisco. Cas9 is a protein enzyme that is capable of cutting strands of DNA, associated with the specialized stretches of CRISPR DNA.

Diagram of the CRISPR prokaryotic antiviral defense mechanism.

Recently, a blockage to the systems was found by researchers which are essentially anti-CRISPR proteins. Before, research on these proteins had only showed that they can be used to reduce errors in certain genome editing. But now, according to Ruben Vazquez Uribe, Postdoc at the Novo Nordisk Foundation Center for Biosustainability (DTU), “We used a different approach that focused on anti-CRISPR functional activity rather than DNA sequence similarity. This approach enabled us to find anti-CRISPRs in bacteria that can’t necessarily be cultured or infected with phages. And the results are really exciting.” These genes were able to be discovered by DNA from four human faecal samples, two soil samples, one cow faecal sample and one pig faecal sample into a bacterial sample. In doing so, cells with anti-CRISPR genes would become resistant to an antibiotic while those without it would simply die. Further studies found 11 DNA fragments that stood against Cas9 and through this, researchers were ultimately able to identify 4 new anti-CRIPRS that “are present in bacteria found in multiple environments, for instance in bacteria living in insects’ gut, seawater and food,”  with each having different traits and properties.  “Today, most researchers using CRISPR-Cas9 have difficulties controlling the system and off-target activity. Therefore, anti-CRISPR systems are very important, because you want to be able to turn your system on and off to test the activity. Therefore, these new proteins could become very useful,” says Morten Sommer, Scientific Director and Professor at the Novo Nordisk Foundation Center for Biosustainability (DTU). Only time will tell what new, cool, and exciting discoveries will be made concerning this groundbreaking system! What else have you guys heard? Comment below!

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