For years, researchers have known that mitochondria (singular: mitochondrion), the tiny "powerhouses" inside each cell that feed off glucose (sugar), are so vital that cancer cells cannot grow without them.
Mitochondrial decline also plays a critical role in aging, and various other diseases.
Now, mitochondrial transplantation has emerged as an exciting new field in regenerative medicine.
It presents a breakthrough, and has the potential to combat aging. Morever, it can help improve health by rejuvenating cellular energy production.
What we know so far:
What are mitochondria?
In cell biology, they are known as the “powerhouses” of cells. They are tiny little organelle inside each of our cells. They do all the energy generation. A person typically has about a 100 mitochondria in his or her cell.
They kind of move around. They combust the glucose and the oxygen.
Mitochondria has been studied for many years. Chemical energy produced by the mitochondria is stored in a small molecule, called adenosine triphosphate (ATP), an energy currency that every cell in our body can use.
ATP is what the cell uses to do everything it does, essentially as a fuel various other cellular processes. They have their own tiny little mitochondrial DNA. While the nuclear DNA has 3 billion base pairs, the mitochondrial DNA is only 16,000 base pairs – which shows how small mitochondria are.
The machinery that the mitochondria use to convert energy is called the electron transport chain.
Mitochondria produce the energy necessary for the cell's survival and functioning.
Mitochondria vs bacteria
They’re very similar in a lot of ways to what you see in bacteria because that's originally where mitochondria came from originally. The theory is that they were bacteria floating around a billion years ago, and they joined in with the DNA and made us humans.
How do mitochondria affect people?
Your cells run on energy.
When you're 20, that's your peak — your mitochondria are in perfect condition, and the mitochondrial DNA is all in perfect shape.
But that declines as we get older.
Mitochondrial decline as we age is one of the underlying reasons for many diseases. It causes all these diseases because there's just not enough energy for the cells to do their job properly.
Bad lifestyle choices, such as a lack of exercise, alcohol, smoking and obesity accelerate this process. A person might also have other reasons for getting diseases, such as predisposition to heart disease, Alzheimer's, or any of these other things like diabetes or arthritis. But the mitochondrial energy decline is the underlying trigger.
How is mitochondrial decline or damage measured?
Understanding of the role of mitochondria has greatly expanded: Latest techniques allow scientists to look at the damage in the mitochondrial DNA, showing the decline over time.
Mitochondria are also now known as key platforms for a whole lot of cell signalling “cascades”, tightly linked to constant reshaping of the cellular mitochondrial network in a series of processes – referred to as mitochondrial membrane dynamics.
Scientists now understand enough so as to almost predict when someone will hit the point where their mitochondria just can’t do the job anymore – that’s when people start to “fade away”.
Ways to measure mitochondrial decline or damage:
- Mitochondrial DNA Analysis: equencing mitochondrial DNA (mtDNA) can reveal mutations and deletions that may contribute to mitochondrial dysfunction.
- Damage assessment: Analyzing mtDNA for signs of oxidative damage, such as base modifications and strand breaks, can provide insights into mitochondrial health.
- Enzyme activity: Measuring the activity of mitochondrial enzymes involved in energy production, such as cytochrome c oxidase and succinate dehydrogenase, can assess mitochondrial function.
- Oxygen consumption: Assessing mitochondrial oxygen consumption rates can provide information about mitochondrial respiration and efficiency.
The role of exercise
One way to boost mitochondrial metabolism: exercise. In the so-called “Blue Zones” — 5 regions of the world with high concentrations of centenarians (Okinawa, Sardinia, Loma Linda, Ikaria, Nicoya Peninsula), a common thread stands out: an active lifestyle. A landmark research led by David Hood, “Coordination of metabolic plasticity in skeletal muscle” (Journal of Experimental Biology, 2006), showed evidence of how exercise training bolsters mitochondrial metabolism.
An acive lifestyle triggers a biochemical process that increases the ATP supply per oxygen molecule (P/O). This “oxidative phosphorylation” is a highly efficient process that boosts mitochondria.
How is mitochondria therapy used to fight diseases?
Scientists are developing techniques to grow healthy mitochondria in "bioreactors" for eventual use in transplants.
This could offer new treatments for heart disease, Alzheimer's, and other age-related conditions, potentially extending both healthspan and lifespan.
What are the benefits of mitochondrial transfer or transplant?
Mitochondrial transplantation has already shown promise in heart surgery and rare childhood diseases, but further research is necessary to refine its techniques and ensure widespread accessibility.
Studies show that mitochondrial transfer promotes tumour invasion and metastasis. Increasing evidence indicates that mitochondrial transfer promotes the invasion and metastasis of tumour cells, which is one of the main hallmarks of tumors.
Researchers now know that mitochondria are so vital that cancer cells cannot grow without them.
(Sources: National Cancer Institute | Journal of Experimental & Clinical Cancer Research)
Studies
Three recent studies on mitochondrial transplantation highlight its potential in treating various conditions, including the treatment of Leigh Syndrome and ischaemic heart disease:
Heart muscle restoration:
A study published in Nature explored how mitochondrial transfer can rejuvenate heart muscle. Transferring mitochondria from a patient's healthy skeletal muscle to damaged, ischemic heart tissue has been shown to restore heart muscle, increase energy production, and improve ventricular function. This process apparently enhances the energy production of cells. Doctors think this process may also facilitate cardiac transplantation by improving heart function post-surgery, potentially increasing the viability of donor hearts.
Cardiac surgeons led by Sitaram Emani, MD, have been testing it as a way to help wean children with congenital heart disease and ischemia-reperfusion injury off extracorporeal membrane oxygenration (ECMO), a pump that pulls the blood outside of the body from one large vein, puts it through a pump which then pushes the blood through a membrane lung that facilitates gas exchange externally. According to researchers who published their work, 16 children have undergone autologous mitochondria transplantation. Of these, 80 per cent were able to come off ECMO, compared with a historical rate of 40%.
Leigh Syndrome:
A new study published on September 3, 2024 in Nature Metabolism shows that mitochondria transfer and transplantation may reduce the morbidity and mortality of Leigh Syndrome, a fatal mitochondrial disease with no effective therapies.
Leigh syndrome is an inherited neurometabolic disorder that affects the central nervous system, and is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951.
Mitochondrial dynamics in health and disease:
Research published in Nature in September 2023 investigated how mitochondrial transfer aids the engraftment of endothelial cells, crucial for vascular therapies. This study also suggested potential applications in developing off-the-shelf mitochondria for widespread therapeutic use.
These studies collectively indicate a growing interest in mitochondrial transplantation as a promising avenue for regenerative medicine, particularly in treating heart conditions.
Mitochondria are passed down from the mother to the child with absolutely no modification.
The nuclear DNA comes from the father and the mother, but the mitochondrial DNA just comes from the mother.
How is mitochondria decline measured?
One technique is via urine sample, which is then run through a mitochondrial DNA scan.
A common way of doing the measurement is to get several strands of mitochondrial DNA (typically 500), which are then sequenced, and laid in a plot. Mitochondrial DNA encodes about 10 or 12 genes. As people age, more “damaged sectors” are detected, like sectors on a hard disk.
So as we get older, our mitochondrial DNA is replicating constantly, and with every replication, there's a chance of a little bit of an error creeping in.
So an old person (>90 years) may have damage score of 25 per cent. A middle-aged person (40-65) may only have an 11 per cent damage score. A young person of between 24 to 30, could only have 7 per cent damage score.
While there are a lot of other pieces of aging, the mitochondrial component has its own aging curve.
What happens when mitochondria malfunction or fail?
Mitochondrial dysfunction has been strongly implicated in glaucomatous neurodegeneration in patients as well as multiple models of glaucoma (eye disease).
Many types of mitochondrial disorders are known. They can affect one part of the body or many parts, including the brain, muscles, kidneys, heart, eyes, and ears.
An imbalance in mitochondrial dynamics can disrupt mitochondrial function, leading to abnormal cellular fate -— and a range of diseases, including neurodegenerative disorders, metabolic diseases, cardiovascular diseases and cancers.
Researchers have studies the effects of changes that occur in mitochondrial dynamics during health and disease, offering new perspectives on how to target the modulation of mitochondrial dynamics.
What does the future hold for mitochondria transfer?
Mitochondrial transfer has faced skepticism—in part because no one really knew why it works. Researchers assumed it was mitochondria going into cells and taking over and generating all of the cell's power. Researchers were surprised they only needed very small amounts of mitochondria for the heart muscle to recover.
A study published in the journal Nature led by Juan Melero-Martin, Ph.D., a researcher in the Department of Cardiac Surgery, found a surprising explanation. The transferred mitochondria trigger the cell to destroy its low-performing mitochondria through "mitophagy" — a kind of cellular housekeeping through "autophagy". This gives cells a better pool of mitochondria, improving their energy and fitness.
Takeaways
Mitochondrial transplantation could have applications in treating heart disease, neurodegenerative disorders, and other conditions associated with mitochondrial dysfunction.
Researchers continue to work in order to fully understand the potential benefits, safety, and long-term efficacy of mitochondrial transplantation.
