Mitochondria Dysfunction The Root Of Your Fatigue

Is Mitochondria Is it the root of all your fatigue and exercise intolerance? 

When you hear Mitochondria you probably think back to your high school biology class and think the “powerhouse of the cell”.   This is true but what goes unrecognized is the magnitude of the impact that mitochondria play on your health.  Here we talk about how mitochondria dysfunction could be causing your fatigue and your exercise intolerance.  

What are mitochondria? 

The mitochondria are present in almost all cells. They are responsible for cellular energy production and they are the gatekeepers of cell death. Mitochondria are integral for energy production. They produce ATP (Adenosine Tri-Phosphate) the energy used by the cells. The root of metabolic dysfunction is in the mitochondria. [1]  

How Do Mitochondria Create Energy?

The answer: Aerobic Respiration/Cellular Respiration 

Mitochondria generate ATP during a process called cellular respiration. This process is where our body combines food and oxygen to generate ATP.  Cellular respiration is a complex process to make it easier to understand it has been broken into a three-part process.  

  1. Glycolysis 
  2. Krebs Cycle (aka Citric Acid Cycle) 
  3. Oxidative Phosphorylation

 This picture shows glycolysis, the Krebs cycle, and the electron transport chain which will be described below.   Yeah crazy! Don’t worry this article is going to break down the process and simplify it for you.

Image Credit: This image is from Peter Attia’s blog , which is a fantastic resource for health information and the podcast is top notch.  I pay monthly to listen to this podcast and it is worth every penny and then some.  

1. Glycolysis & Beta Oxidation 

Carbohydrates (Sugar) 

To begin to produce energy from sugar/carbohydrates the body uses glucose and extracts pyruvate.  When the body has enough glucose and proper insulin sensitivity the brain will convert glucose to pyruvate, this process is called glycolosis (and occurs in the cytosol). The cytosol is inside the cell but outside the mitochondria. Pyruvate is shuttled into the mitochondria and converted to acetyl CoA by the enzyme pyruvate dehydrogenase.   

Fats and protein are oxidized in a different manner. Fatty acid oxidation is a whole separate subject so it will only be touched upon lightly.


Beta oxidation is when fatty acids are broken down to create energy. Fatty acids are converted to acetyl-CoA inside the mitochondria.


For protein, there are various enzymes exist for the conversion of specific amino acids into pyruvate, acetyl-CoA or directly into particular citric acid cycle intermediates. [2]

Supplement note: L-carnitine is used to shuttle acetyl CoA from cytosol into mitochondria 

Sugar, fats, and proteins need to be converted to acetyl CoA because Acetyl CoA begins the  Krebs (aka citric acid cycle) which take place in the mitochondria. 

2. The Krebs Cycle 

The Krebs Cycle is where the mitochondria takes the acetyl CoA and begins to create ATP through a series of enzymatic systems.

When acetyl CoA  (two carbon) is combined with oxaloacetate (4 carbon molecule) the Krebs Cycle begins.  The two-carbon acetyl group of acetyl-CoA is transferred to the four-carbon oxaloacetate, forming the six-carbon molecule citrate. The citrate is oxidized back to oxaloacetate in a series of seven enzymatic steps, with the excess carbon carried away as two molecules of carbon dioxide and the electrons removed in the process passed to the cofactors nicotinamide adenine dinucleotide(NADH) and flavin adenine dinucleotide (FADH2). The oxaloacetate is now free to participate in the cycle again, while the free energy liberated is carried by NADH and FADH2 to the mitochondrial electron transport chain. This is how the Krebs Cycle feeds the Electron Transport Chain which then generates ATP.   

3. Oxidative Phosphorylation

The final step is Oxidative Phosphorylation. This consists of two parts the electron transport chain and chemiosmosis. These two processes work together to form oxidative phosphorylation.

A. Electron Transport Chain

The Electron Transport Chain (ETC) is where most of the ATP is produced. It is the only part of glucose metabolism that uses atmospheric oxygen. There are four complexes that make up the ETC (labeled complex I-IV) they move electrons from NADH and FADH2 to molecular oxygen. 

The ETC is where electrons removed from the citric acid cycle by NADH and FADH  are passed from one member of the transport chain to another.

These electrons are passes by redox reactions. Redox reactions are those that transfer electrons e.g. electron donors to electron acceptors. Energy released in these reactions is captured as a proton gradient, which is then used to make ATP in a process called chemiosmosis. 

B. Chemiosmosis 

Chemiosmosis is the mechanism that allows ATP to be exported into the cytosol to be used as energy. As well as, importing ADP into the mitochondria where cells change ADP (di-phosphate) to ATP (tri-phosphate).

The mitochondrial ADP/ATP carrier is one of the most abundant proteins of the mitochondrial inner membrane. This provides the first and last transport step in oxidative phosphorylation, as it imports the spent fuel ADP back into the mitochondrion for ATP synthesis and exports the synthesized ATP out of the mitochondrion for use in the cytosol. 

How Chemiosmosis works:

ATP produced inside the mitochondria is picked up by translocator proteins (ATP synthase). Translocator proteins sit on the surface of the mitochondria. They move ATP out into the cytosol where it energizes the cells.  The ATP is converted to ADP when the energy is consumed. ADP passes back into the mitochondria by the translocator protein and is converted back into ATP by oxidative phosphorylation   [3]


Supplement note: Magnesium and CoQ10 are important for this process of driving chemiosmosis.  

Calcium Signaling 

Mitochondria are in constant communication with the cytosol to coordinate the balance between the energy demands of the cell and energy production by oxidative phosphorylation. This is calcium signaling between the cytosol and matrix. 

How Much ATP is Made From One Glucose?  

Note if oxygen is not present, or not utilized, anaerobic respiration will occur. Anaerobic means glucose is converted directly to lactic acid.  Anaerobic nets only 2 ATP where Aerobic respiration nets 32-36 ATP. To add, once converted to lactic acid it takes 6 molecules of ATP to convert lactic acid back to glucose.  This is why you will see a buildup of lactic acid in people suffering from mitochondrial dysfunction.  

Signs That You Mitochondria Aren’t Working 

Poor Stamina & Exercise Intolerance 

Poor stamina is when you can only do things for a short amount of time.  The cause of this could be the poor recycling of ATP.  

Delayed Fatigue & Post Exertional Malaise 

Post Exertional Malaise (PEM) occurs when you engage in stressful activity and the next day you feel like complete trash. It’s not normal tiredness, but an overwhelming collapse in you body.  The stress could be work, personal life, excessive cardio, or intense interval workout. The hypothesis is that the event has stressed the mitochondria and used up all the ATP.

In this situation, when a cell is stressed and there is not enough ATP the body will use ADP for energy.  When ADP is used for energy it gets converted to AMP (mono-phosphate) and AMP cannot be recycled. At this point, ATP must be newly generated from fresh nutrients and it takes 1-4 days to create brand new ATP.   

Ways To Support Your Mitochondria


Follow a paleo style or autoimmune style diet. Resources on Auto-Immune Paleo.


  • CoQ10
  • Pqq
  • Vitamin C
  • Alpha Lipoic Acid

Redlight Therapy

This has been one of the most beneficial tools for me regaining health. I use the Joovv. I slowly started with only a few minutes a day. Gradually increased to 10 -15 minutes. I now use it every day and it has been extremely beneficial for my energy and combating Fatigue.

Zone 2 Training

Only attempt zone two training if you have boosted you energy and the amount of steps you can take. I didn’t attempt zone two training until I could consistently walk 10,000 steps per dy.


Grounding is how it sounds you are literally connecting yourself with the earth. You can do this by walking around barefoot or by purchasing grounding mats. It sounds a little out there but it works. Why do you think everyone falls asleep on the beach. Read this journal article on grounding and its effects on the immune system and inflammation here

Here is a snippet: Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing) produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. …Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response.



[1] Mitochondria And Metabolic Dysfunction [Back To Text]

[2] Protein Synthesis [Back To Text]

[3] Recycle ADP & ATP [Back To Text]

[4] The effects of grounding (earthing) on inflammation, the immune response [Back To Text]