Mitochondrial diseases are a broad category of diseases that have many different symptoms and appearances. They can be mild or severe.
Mitochondria are the powerhouse of the cell, but they’re also, in my opinion, the coolest part, aka organelle, of the cell. An organelle is a specialized part of the cell, including the mitochondria, Golgi apparatus, ribosomes and more. Mitochondria produce the energy your body needs to function. There are mitochondria in almost every cell of your body (except red blood cells). Because they are in so many different cells, mitochondrial diseases can have dramatically different symptoms based on what organ system is impacted. That probably sounds a little confusing right now, so we’re going to do a deep dive into some biochemistry and some genetics before we talk about mitochondrial diseases generally.
Nuclear and mitochondrial DNA
DNA, deoxyribonucleic acid, is the instruction manual your body uses to create proteins. It lives in the nucleus of every one of our cells (except red blood cells, which don’t have a nucleus). It is also copied and replicated whenever a new cell is made. This type of DNA is called nDNA because it lives in the nucleus. I think of the nucleus as the brain of the cell. Mitochondria themselves also have their own sets of DNA, which is called mitochondrial DNA or mtDNA for short. Mitochondria have their own DNA because they can replicate on their own, without the entire cell creating a copy of itself.
Mitochondrial diseases can happen due to two different types of errors in DNA.
A mutation is like a tiny “typo” or change in the genetic instructions (DNA) that tell a cell how to work. When a mutation happens in our instruction manual, the DNA, sometimes the body still understands what is written and can make normal proteins, but sometimes it’s a huge typo and the proper protein can’t be made. In mitochondrial diseases, there is either a mutation in the nuclear DNA or in the mitochondrial DNA. If the mutation is in the mitochondrial DNA, these disorders are called “primary” mitochondrial disorders. If the mutation is in the nuclear DNA, it may impact proteins that help the mitochondria function which may cause problems. Where the mutation is, mtDNA or nDNA, will impact how the mutation is passed on to children.
If the mutation is in the mtDNA, all children of an impacted mother will be impacted. If the mutation is in the nuclear DNA (nDNA), then how children are affected depends on whether the mutation is recessive or dominant. We have two copies of every gene (one from each parent) and a dominant mutation means that only one copy of the gene is changed for symptoms to appear. In recessive mutations, both copies of the gene need to be mutated for symptoms to appear.
But mitochondria are even more complicated…
Fun fact: You get all your mitochondrial genetics from your mother. (Okay, not all! Recent research shows that fathers do contribute to our mitochondrial inheritance, but not much.)
What is “mitochondrial heteroplasmy”?
Mitochondrial diseases can look very different from one person to another person. Scientists call these differences “phenotypes.” This happens because of a genetic concept called mitochondrial heteroplasmy, which means a person can have a mixture of mutated and healthy mitochondrial DNA. In other words, not all the mitochondrial DNA in your body has to be exactly the same. Some can carry the mutation and some might not. Mutations can either be germline (mostly from the egg that formed you, but remember that sometimes the sperm can contribute mitochondria as well) or somatic (a random mutation in a dividing cell after you’re born, like a skin cell).
Here’s an example: imagine a developing fetus that starts as one cell which divides into two, those two divide and then it’s four cells and the cells keep dividing. If one of those cells gets a mitochondrial mutation, all the cells that grow from that cell will have the mutation. The cells that don’t come from that mutated cell will still be normal. So if those mutated cells become eye cells, the baby might only have eye problems and the rest of the body doesn’t have symptoms.
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(Source: drawing by Rebecca Raskin-Wish)
That was a simple example, and our bodies are a little more complicated, but it helps us understand why mitochondrial diseases can look so different.
What do mitochondrial diseases look like?
Mitochondrial diseases are very rare and look very different from person to person. For example, one person might have symptoms in one part of the body, like their eyes, and another person can have symptoms that impact their entire body. Testing for mitochondrial diseases can be very complex if the diseases are suspected. Some examples of mitochondrial diseases include:
🔸 Myoclonic epilepsy with ragged red fibers (MERRF)- a very rare condition that causes seizures, muscle problems, heart arrhythmias, hearing loss, vision loss, and ultimately dementia. MERRF symptoms begin in childhood. It’s important to note that the symptoms can be very different based on how much mitochondrial heteroplasmy there is, which can make it very hard to diagnose.
🔸 Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS)- temporary muscle weakness or paralysis that looks like a stroke, decline in cognitive abilities, headaches, seizures, heart disease, and diabetes.
🔸 Neuropathy, ataxia and retinitis pigmentosa syndrome (NARP)- rare condition that causes numbness and tingling in arms and legs, balance problems, vision loss, and exercise intolerance.
🔸 Leber hereditary optic neuropathy (LHON)-this syndrome can appear around the ages of 20 to 30 with blurred vision, a central blind spot in the eye, and difficulty reading or recognizing faces due to vision loss.
🔸 Leigh syndrome- This occurs in babies and can cause loss of developmental milestones, seizures, frequent vomiting, problems swallowing and loss of muscle tone, vision loss, and difficulty breathing
This list contains only a few examples of mitochondrial diseases and is not at all exhaustive. You can read more about the different types here. Again, these conditions are very rare.
Nerd Alert: Where did mitochondria come from?
One of the main theories about how we evolved mitochondria is based around the idea of symbiosis, which is when two organisms help each other out. The thought is that our early one-celled ancestors swallowed a bacterium. The bacteria were protected from the elements and the single-celled organism received extra ATP. They worked so well together that the bacterium evolved to become a mitochondrion and we still have mitochondria in our cells today!
Bottom line: Mitochondrial diseases are a broad category of complex diseases that can all look really different.
