The Cases of Diseased Organelles- Mitochondria

You are cells. Cells are the basic units of structure and function in all living organisms. Inside cells, there are organelles, which are similar to “tiny organs” that help a cell function by performing jobs they are responsible to complete. When these organelles become diseased, problems arise. Welcome to The Cases of Diseased Organelles #1: Mitochondria and the Brain.

Mitochondria, the "powerhouse" of the cell.

The mitochondrion is home to the “energy factory” of a cell. It is an oval-shaped membrane-bound organelle found in almost all eukaryotic cells. A mitochondrion is special compared to many other organelles a cell might have because it is double-membraned, and it has its own DNA, also known as mtDNA. As the energy factory, the mitochondrion generates large quantities of energy in the form of adenosine triphosphate (ATP). Although generating energy is the most well-known function of mitochondria, mitochondria also store calcium for cell signaling activities, generate heat as part of the energy, and mediate cell growth and death. With so many functions, even a little “trip” off the stairs can cause a multitude of diseases.

Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are two of the most common diseases caused by mitochondrial dysfunction. As the brain needs a lot of energy to function, mitochondria are key to well-functioning brain and neuronal systems. Alzheimer’s is a neurological disorder in which thinking and memory become impaired. First described by Dr. Alois Alzheimer in 1906, he noticed that the brain of a patient who lost cognitive function before death had clumps and fibers, also known as amyloid plaques today, and neurofibrillary tangles. Dr. Alois Alzheimer’s observations of the brain were unprecedented, marking the discovery of this new disease. Often, AD is caused by old age as there are reductions in cytochrome-oxidase (COX) subunits II and IV. COX is the enzyme protein in mitochondria. Reductions in COX subunits are not uncommon; rather, they are a normal part of the aging process, which is why older people are at greater risk for developing Alzheimer’s. Aging plays a major factor in Alzheimer’s. Mitochondria dysfunction is classified as an early event in AD, in which Aβ deposition, synaptic degeneration, and Neurofibrillary tangles (NFT) formation are categorized as pathological hallmarks and lesions of AD. When the following hallmarks are present in one’s brain, it is an indication of Alzheimer’s. Synaptic degeneration is the spreading of damaged neurons to other neurons that worsen the brain’s conditions. Additionally, patients who are diagnosed with Alzheimer’s are found with less mtDNA. In many cases, up to 28 percent of mtDNA is lost. Not only so, but oxidative stress also plays a causative role in the origination and development of Alzheimer’s. Oxidative stress is another result of aging. When there is oxidative stress, oxygen species, or free radicals, and antioxidants experience cellular imbalance. In cases of imbalance, excess free radicals damage other molecules such as DNA and proteins and eventually lead to disease and cancer. The mitochondrion is more vulnerable than other organelles to oxidative stress and the cell’s inability to repair the damage caused worsens and speeds up the development of Alzheimer’s. Currently, a treatment to cure Alzheimer’s has not been discovered yet, but there are options to manage symptoms and slow down the progression of this neuron degeneration disease.

While Alzheimer’s is a neurological disorder that mostly affects thinking and memory, Parkinson’s is a neurological disorder that mainly affects movement. Parkinson’s is caused by mitochondrial dysfunction in the substantia nigra (SN). The SN is a “midbrain dopaminergic nucleus” responsible for dealing with dopamine and its transmitters. It plays a prominent role in regulating movement, which is why any mitochondria malfunction in the SN can lead to Parkinson’s. In patients that are diagnosed with Parkinson’s, mtDNA is also deleted along with losses in ATP provision and calcium buffering capacity. Besides deletion and losses, mitochondrial interactions with other organelles are also reduced and there is degradation through mitophagy, in which the mitochondria “self-eats” themselves, similar to autophagy. Possible causative factors for Parkinson’s include the distribution and structure of mitochondria, but more studies have to be conducted for clearer conclusions. The process of neurodegeneration of the brain in Parkinson’s patients is also elusive. Similar to Alzheimer’s, there are no cures for Parkinson’s yet, but there are choices to control symptoms and maintain one’s quality of life.

Mitochondria are essential to the health of a cell. Even the smallest mutations that the body does not catch and other dysfunctions may cause diseases to start developing in the human body. Alzheimer’s and Parkinson’s are merely two common mitochondrial diseases, and so much is yet to be discovered regarding mitochondrial diseases, especially courses of treatment. Support your mitochondria by staying healthy and eating enough protein, for mitochondrial health is part of what it means to be well and alive.

Credits:

Biology I-- How do diseases affect humans at the cellular level? docs.google.com/presentation/d/1fLSBzliROh_fbOghLld8idaBUgKn9i36yYxLPh0yGFU/edit#slide=id.gf67904d0f7_0_13.

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