Posted on June 10, 2019 at 11:00 PM
The process of converting food and oxygen (fuel) into energy requires hundreds of chemical reactions, and each
chemical reaction must run almost perfectly in order to have a continuous supply of energy. When one or more
components of these chemical reactions do not run perfectly, there is an energy crisis, and cells cannot
function normally. As a result, the incompletely burned food might accumulate as poison inside the body.
This poison can stop other chemical reactions that are important for cells to survive, making the energy crisis
even worse. In addition, these poisons can act as free radicals (reactive substances that readily form harmful
compounds with other molecules) that can damage the mitochondria over time, causing damage that cannot be
reversed. Unlike nuclear DNA, mitochondrial DNA (mtDNA) has very limited repair capabilities and almost no
protective capacity to shield the mitochondria from free radical damage.
Many mitochondrial components are encoded by nuclear DNA rather than mtDNA; thus, mitochondria must have
mechanisms to take up their components from the surrounding cytoplasm. The mitochondrial proteins encoded by
nuclear genes that are made outside of the mitochondria are transported in by specific machinery found in the
Compounds that mitochondria require to function properly include the following:
Coenzyme Q10 (CoQ10)
- B vitamins
- Alpha lipoic acid
- Thyroid hormone (T3 and T2)
For more information about these compounds and more, please see the section “For the Scientist, “ and “For a Better
Mitochondria”. Please see your haplogroup for specific recommendations on dosages.
For the Scientist: The vast majority of mitochondrial proteins are synthesized from nuclear genes and
transported into mitochondria. These include the enzymes required for the citric acid cycle, the proteins
involved in DNA replication and transcription, and ribosomal proteins. The protein complexes of the respiratory
chain are a mixture of proteins encoded by mitochondrial genes and proteins encoded by nuclear genes. Proteins
in both the outer and inner mitochondrial membranes help transport newly synthesized, unfolded proteins from the
cytoplasm into the matrix, where folding ensues (for example, please see below image).
As mentioned above, mitochondrial compounds that are required for proper mitochondrial function include the
CoQ10 is a fat-soluble substance that functions as an electron carrier; hence its position within the
inner mitochondrial membrane. It has three reduced states, ubiquinone, semiquinone, and ubiquinol.
Ubiquinol is better absorbed and is thus the optimal form of CoQ10 for supplementation.
B vitamins function as enzyme cofactors in each step of the tricarboxylic acid (TCA) cycle and within
the ETC. B vitamins can quickly become depleted in individuals on a diet consisting of mainly processed
grains, as these grains provide glucose but are stripped of bran and germ, which contain B vitamins to
help our bodies obtain energy from glucose. B vitamin deficiencies are also very common in individuals
with an imbalance in their gut flora, such as small intestinal bacterial overgrowth (SIBO) or candida
Carnitine shuttles fatty acids into mitochondria for use as energy. It is synthesized in the body from
lysine and methionine and is also obtained through eating meat, especially red meat. Carnitine has been
found to improve the function of the TCA cycle and electron flow through the ETC. Carnitine
supplementation can help ameliorate dementia and cognitive impairment associated with mitochondrial
dysfunction. In fact, acetyl l-carnitine has been reported to improve cognition in individuals with mild
cognitive impairment and mild Alzheimer's disease. Acetyl l-carnitine is the form of carnitine that
crosses the blood-brain barrier, so it's preferred when the support of cognition is the goal.
However, carnitine deficiency has been shown to cause delayed gut motility, leading to vomiting after meals,
oral drooling, delayed gastric emptying and constipation. This makes sense considering the extent to which
muscle function is impacted by mitochondrial function and optimal gut motility is a consequence of healthy
Ribose is a five-carbon sugar made from glucose in the body. It's a component of ATP and NADH/NAD+.
A mouse study has found that ribose increases gut motility and improves resistance to weight gain
through improved energy homeostasis. Supplementation with D-ribose has also been demonstrated to be
helpful for chronic fatigue and fibromyalgia patients, as it promotes increased cellular energy.
Moreover, ribose may provide protection to cells under elevated oxidative stress.
Alpha lipoic acid (ALA) is a fatty acid that is synthesized within mitochondria, and it acts as a very
potent antioxidant. It can also be obtained from the diet in the form of lipoyllysine and is highest in
animal tissues (kidney, heart, and liver) and in green plants, such as spinach and broccoli. In addition
to being an antioxidant, ALA is also a necessary cofactor for one of the enzyme complexes that make up
pyruvate dehydrogenase. This enzyme complex converts pyruvate (made from glucose) to acetyl-CoA, which
is the entrance point for the TCA. Although our bodies typically make enough ALA, supplementation has
been shown to support brain health, cardiovascular health, heavy metal chelation, insulin function, and
inflammation. ALA has repeatedly been shown to work well when supplemented together with acetyl
Thyroid hormone is often overlooked for it's a vital role in mitochondrial function. There are several
forms of thyroid hormone, thyroxine (T4), triiodothyronine (T3), 3,5 diiodo-l-thyronine (T2) and
monoiodothyronine (T1). Each of these forms is named based on the number of iodine atoms attached to
them. T3 and T2 play important roles in mitochondrial function. T3 is often called "active" thyroid
hormone because it's necessary for the function of every cell within the body. T3 acts as a transcription
factor, turning on certain nuclear genes that contribute to cellular function. T3 and T2 work in a
similar manner within mitochondria; they turn on mitochondrial genes that code for key proteins with the
See Making Mitochondria Better for information on what Mitochondria need for growth and optimization.