TheLabMix

Hi there, it's fantastic you're doing this AMA and getting some awareness out into the world for Mitochondrial diseases. I did my PhD in mitochondrial biology studying mitochondrial gene expression, if you have any scientific questions, although you seem very well-versed as is!

Have you gotten a genetic diagnosis? Do you know if your mutation is in mtDNA or nDNA? In the UK, there were several mitochondrial units that regularly did genome sequencing in order to pin down the exact genetic mutations that were causing the patient's mitochondrial disease. Which is not to say we always knew HOW the lesion was affecting mito physiology, but it fueled much of the research we did. Are you involved with any research efforts? Much of the difficulty in treating these types of disorders is the lack of ability to manipulate the organelle itself in an experimental context. Towards that end, patient samples play a HUGE role in research, because they may carry mutations that we as researchers couldn't otherwise engineer in the lab. So mitochondrial research owes a massive debt to the patient community. So thank you for your outreach, and linking to donation pages. Hope you keep going strong!

Fortunately, you are not being BS'd! So MFN2 is a nuclear gene that encodes a protein called mitofusin-2. This protein is essential for fusion of individual mitochondria in the cell. Unlike how textbooks portray mitochondria, they are not single bean-shaped organelles floating around the cell. They are highly dynamic, reticulum-like structures. Think of them like a huge network wired throughout the cell, constantly coming apart and then refusing together. This process allows organelle movement, transfer of materials within the mitochondria, etc. So it's very important to mitochondrial function. If the process is impaired, you can have major consequences.

As to the sperm issue, it is true that essentially all of the mitochondria you inherit are maternal. But the mitochondrial genome only encodes 37 genes, all of which either encode subunits of the electron transport chain, or are involved in its construction. Mitochondrial DNA only encodes around 0.1% of the total mitochondria proteins, so the vast majority of genes related to mitochondrial function are encoded in the nucleus. This is how you can inherit mutations from your father, they reside in the nuclear genome, not mtDNA. Mitochondrial diseases can have really varied presentations too, so that is how you sometimes get only certain family members showing pathology.

Dang, CHOP has a new large mitochondrial group headed by Doug Wallace, a major mito scientist who came from UPenn I believe. I'm sure they would have been able to shed some light on your condition. Especially if it's novel. If your sample was sent for sequencing, then maybe that info is still out there! Unfortunately, as you already know, identifying the mutation rarely produces insights for clinical treatment. We just don't have many options for mitochondrial disorders.

Mitochondrial research is fairly unique in that it not only serves patients, but relies on them as well. So you deserve just as many thanks. It's a great community, in that patients, physicians, and scientists often work closely together.