Testing for Mitochondrial Function: Optimize Your Cells' Health

Dec 28, 2023 | Written by Matthew Lees, PhD | Reviewed by Scott Sherr, MD and Marion Hall

Testing for Mitochondrial Function: Optimize Your Cells' Health

As the mitochondria are the batteries of our cells and play an important role in our health, it’s only right that we keep them in top condition. Testing methods are one way to accomplish this!

Mitochondria are tiny organelles in the cells of the body that could be described as the powerhouse of the cell [1,2], in that they generate the energy (adenosine triphosphate or ATP) that allows cells to function. They vary in size and structure but tend to be only a couple of square micrometers when viewed cross-sectionally [3].

Interestingly, mitochondria possess their own DNA separate from that found in the cell nucleus. They essentially convert the food we eat into energy in the presence of oxygen, a process called aerobic respiration. The biochemical reactions that produce ATP are called the Krebs cycle and oxidative phosphorylation [4,5].

Although their main role is in generating ATP, mitochondria also help regulate cellular metabolism [2], immune system signaling [6], steroid synthesis [7], hormonal signaling, calcium storage, and programmed cell death [8].

Given these wide-ranging and highly important roles, mitochondrial problems can have a tremendous impact. Many genetic and non-genetic diseases and health conditions involve the mitochondria, due to their far-reaching influence on cellular metabolism.

In today’s article, we are going to talk about why mitochondria are so vital, discuss some of the problems that can emerge, and examine current methods of testing for mitochondrial function. We will also assess how these testing methods can be used to support optimal health and well-being.

Mitochondrial Disorders and Their Impact

Mitochondrial diseases are one of the most common inborn errors of metabolism, with conservative estimates suggesting a prevalence of 1 in 5,000 [9]. Primary mitochondrial disorders are defined as disorders that affect the structure and function of mitochondria due to mutations in either the nuclear or mitochondrial DNA.

As the mitochondrial respiratory chain is the final step in aerobic respiration, any tissues and organs with a significant dependency on aerobic metabolism, requiring high amounts of energy, are preferentially involved in mitochondrial disorders [10,11]. Symptoms of these disorders are heterogeneous, affecting multiple organ systems, and it is this heterogeneity that makes clinical diagnosis a real challenge.

People who inherit a mitochondrial disease tend to have a relatively normal early life, then develop symptoms during childhood, mid-life, or old age depending on the severity of the mitochondrial DNA mutation (inherited maternally), and then progressively decline [10,12]. The accumulation of age-associated mitochondrial DNA mutations further compounds the problem.

Although there is no cure for primary mitochondrial disease, dietary supplementation can help and there are many ongoing clinical trials [4].

What is the “Gold Standard” Testing Method for Mitochondrial Function?

To confirm the existence of mitochondrial disease, extensive clinical and laboratory evaluation is required, using a multi-pronged approach [4,13]. This is particularly the case in establishing a specific molecular diagnosis, whereby blood and tissue samples are needed for analyte measurements, histology (looking at cross-sections under a microscope and staining for different targets/proteins), neuroimaging, enzyme activity tests, and DNA analysis [14].

Generally, a muscle biopsy provides the best opportunity to assess aspects of mitochondrial function [15]. During this process, an area of interest is selected and sterilized. After a local anesthetic is injected around the site, a piece of muscle tissue (around 100 mg) is surgically removed and prepared for analysis using a range of methods. This technique has been used thousands of times in a range of populations and has a very low minor complication rate of 0.15% [16,17]. From this muscle tissue sample, activity measurements can be made for individual oxidative phosphorylation (electron transport chain) enzymes.

Although sampling of muscle and other tissues has been described as a “gold standard” method, newer technologies such as next-generation sequencing using blood, urine, or tissue to comprehensively analyze the mitochondrial genome appear to have taken up this mantle [9,18,19]. Blood and urine metabolites can serve as a rapid first-screening approach when mitochondrial disease is suspected, followed by first-line clinical molecular genetic testing to determine the diagnosis [4]. Biopsies can then be reserved for clinically urgent cases given their invasive nature, or to confirm an inconclusive genetic testing result.

The Organic Acid Testing Method

The organic acid test is one option for assessing mitochondrial function [20]. It looks at the metabolites from the digestion of food as well as ATP generation within the mitochondria using a urine sample, as these compounds are more easily extracted from this medium than blood plasma [14]. Such a metabolic panel might include several dozen metabolites from the analysis.

A lab test such as this can highlight the location of inefficiencies or problems within the metabolic pathways and help direct treatment strategies for the best effect. This is especially true in young populations including children [21]. For instance, elevated levels of lactate in the urine and/or ketone bodies (breakdown products from fats) can assist in the diagnosis of mitochondrial disease without the need for invasive procedures such as biopsies [21].

Common Medications that Impact Mitochondrial Function

Various common drugs can interfere with the healthy function of mitochondria, such as statins, anti-diabetics, anti-epileptics, NSAIDs, anti-depressants, and certain antibiotics. The mechanisms for this are varied but involve stimulating the opening of the mitochondrial permeability pore, inhibiting the mitochondrial respiratory chain, stimulating phosphorylation uncoupling, and damaging mitochondrial DNA [22].

If you’d like to learn more about medications that enhance (and medications that destroy) your mitochondrial function, read here!

How Are Common Diseases Linked with Mitochondria?

Common diseases, such as type II diabetes (T2DM), affect mitochondrial function. Focusing on T2DM, it has been proposed that the insulin resistance typical of T2DM is caused by mitochondrial dysfunction. The main mechanisms for this include reduced oxidative phosphorylation, mutations in mitochondrial DNA, and impaired pancreatic beta-cell function [23].

Lifestyle Factors that Affect Mitochondrial Function

Mitochondria are affected by several behaviors and lifestyle factors, both within and outside our realm of control. They are susceptible to reduced nutrient availability (suboptimal food consumption), toxins in the environment (such as metals), oxidative damage, aging, and alcohol consumption. To illustrate, alcohol consumption depletes the NADH needed for ATP production in the mitochondria, thus increasing the production of damaging reactive oxygen species [24].

Want to optimize your mitochondrial function and accelerate your energy production? Perhaps master your mitochondrial health? Read here and here!


In this article, we have addressed the importance of mitochondria in health and disease, mainly for their roles in energy production and regulating cellular metabolism. We have also highlighted how things can go awry in the case of genetically inherited mutations in mitochondrial DNA, and how this can manifest as primary mitochondrial disorders.

We also provided some background on the types of testing methods used to ascertain mitochondrial function and the efficiency of the biochemical pathways involved. Although muscle tissue biopsies were regarded as the “gold standard” method, newer techniques such as organic acid testing can be a rapid first-line assessment to inform the clinical management of a given case.

Lastly, we discussed common medications, diseases, and lifestyle factors that have relevance to mitochondrial function and how they can affect it to one degree or another.

If you're looking for a quick way to really boost your mitochondria's ATP production, then check out Just Blue, our methylene blue troche for pure cellular revitalization.

If your mitochondria need some immediate support, then find a practitioner and try Tro+ Blue to bolster your health armor in the face of physiological challenges.



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