EVERYTHING ABOUT
Mitochondria
Every week I am posting about everything you need to know about hormones. This weeks topic is about Mitochondria
Did you know …
- Are minuscule specialised structures within a cell known for its energy-generating capabilities – aka they are the powerplants of the cells
- Absolutely everything that happens in the body, each and every muscle contraction, biochemical cascade, cellular regeneration, detoxification etc requires energy. Nothing can occur without energy.
- They are the shape of a bean and often form networks with each other.
- They produce up to 90% of the body’s energy called ATP – Adenosine-Tri-Phosphate from the foods we eat.
- They use a process called aerobic respiration, ie they use oxygen to create ATP energy.
- They are considered to be bacteria and have their own DNA.
- The symbiotic relationship with the cells of the body was created approx. 2 billion years ago when an single cell organism cell acquired the mitochondria bacteria.
- This new single cell organism was now able to use oxygen as fuel, which was previously toxic to the cell and enabled the cells to evolve.
- Antibiotics may cause mitochondrial dysfunction, which may contribute to chronic disease.
- Mitochondrial DNA is only passed on maternally, ie. from the mother.
- They are found in all cells except mature red blood cells which need room to carry oxygen.
- Different types of cells have different numbers of mitochondria fx liver cells can have up to 2000 mitochondria and heart muscle cells up to 5000 and a nerve cell / neuron an estimated 2 billion.
- They can quickly change shape and move around the cell as and when needed.
- When the cell needs more energy, the mitochondria can reproduce by growing larger and then dividing.
- They also help the immune system detect foreign pathogens and defects within the cell.
- They initiate a process called apoptosis which leads to the death of the cell and elimination from the body.
- As we age mitochondrial function decreases which is the hallmark of both aging and most chronic disease.
- Even asymptomatic people in their 30s can have significantly decreased mitochondrial function and early onset mitochondrial dysfunction is indicative of premature aging and future health problems.
- When it comes to health and disease prevention mitochondrial health and function cannot be overstated.
- If your mitochondria are not functioning well, nothing else will either.
- They were first discovered by Albert von Kölliker in 1857.
- The term mitochondria was coined by Carl Benda in 1898.
- The nickname the “powerhouse of the cell”, was coined by Philip Siekevitz in 1957.
Meet Sally and get to know all about Mitochondria
Mitochondria 101
ATP production
Mitochondrial jobs
What screws up mitochondria
Mitochondria 101
- Is a double-membrane-bound organelle found in most multi celled organisms.
- Generates most of the ATP/adenosine-tri-phosphate aka cell energy from the diet by using the energy of oxygen in the inner mitochondrial membrane.
- They were first discovered by Albert von Kölliker in 1857.
- Some cells lack mitochondria eg. mature red blood cells.
- Mitochondria are commonly between 0.75 and 3 μm2 (square micrometres) but can vary considerably.
- The number of mitochondria in a cell can vary widely by organism, tissue, and cell type.
- A mature red blood cell has no mitochondria.
- A liver cell can have more than 2000.
- A heart muscle cell can have more than 5000.
- A neuron can have more than 2 billion.
- In addition to supplying cellular energy, mitochondria are involved in other tasks, such as cell signalling, cellular differentiation, and cell death, as well as maintaining control of the cell cycle and cell growth.
- Mitochondria have been implicated in several human disorders and conditions, such as neurological diseases, cardiac dysfunction, heart failure and autism.
- The mitochondrion is composed of compartments that carry out specialized functions.
- Outer membrane – is a selective barrier to molecules from the cytoplasm, such as Ions, nutrient molecules, ATP, ADP.
- Inner membrane – is folded and performs a number of functions to help make energy. The electron transport chain is situated in the membrane.
- Cristae – The name of the folds on the inner membrane, which increase its surface area.
- Inner membrane space aka the matrix is the space inside the inner membrane which contains most of the proteins, ribosomes and mitochondrial DNA.
- The mitochondrial DNA the “mitogenome” is very similar to bacterial genomes.
- Mitochondrial proteins made from mitochondrial DNA vary depending on the cell and tissue type.
- In humans, 615 distinct types of proteins have been identified from cardiac mitochondria.
- They can quickly change shape and move around the cell as and when needed.
- When the cell needs more energy, the mitochondria can reproduce by growing larger and then dividing.
- If the cell needs less energy, some mitochondria will die or become inactive.
Mitochondria’s Many Jobs
- Produce energy / ATP
- Produce heat – during ATP production – the hottest organ is the rectum
- Produce CO2 and water as waste products from ATP production
- Produce ROS / free radicals – during ATP production
- Programme cell death
- Control calcium levels – calcium is stored and released by the mitochondria
- Produce steroid hormones – in steroidogenic cells of the adrenal, gonad, placenta and brain.
Energy production in a nutshell
- ATP– adenosine-tri-phosphate is the energy currency within the body.
- Most ATP production takes place in the mitochondria – via a long chain of reactions, in all cells apart from mature red blood cells.
- Production is dependent on the availability of various nutrients, vitamins and minerals.
- Produced from glucose directly via glycolysis and via Acetyl-CoA created from the breakdown of fats, proteins and glucose.
- Glycolysis occurs in the cytosol (cell fluid) and doesn’t need oxygen to produce small amounts of ATP.
- The conversion of Acetyl-CoA to ATP occurs in the mitochondria which does require oxygen.
- ATP production occurs in 3 steps where the biggest production of ATP occurs in the 3rd part, but you got to go through the first 2 parts to get to the 3rd part.
- The production of Acetyl-CoA is the first step.
- Acetyl-CoA is end molecule from glucose, fat and protein metabolism which requires oxygen.
- Ketones can also produce Acetyl-CoA.
- Once you have Acetyl-CoA you enter the 2nd part – the so called Krebs cycle which needs B vitamins and amino acids.
- The purpose of the Krebs cycle is to transfer high energy electrons to the 3rd part using the carriers molecule NADH and FADH2 which are produced in the Krebs cycle.
- In the 3rd part – the electron transport chain, things get more complicated and where most dysfunction can occur.
- In this part you need CoQ10 and hydrogen ions to supply electrons (which it gets from the Krebs cycle).
- NADH and FADH2 pass through various electron transporters or complexes embedded in the inner mitochondrial membrane shuttling electrons into the complexes.
- On route the shuttling of electrons moves protons into the inner membrane space /the matrix of the mitochondria.
- Protons have a positive charge which builds up creating an electrical potential strong enough to create ATP – picture the force or energy in a balloon.
- On route ROS/free radicals are be produced, which can damage mitochondrial DNA.
- Any time free radicals exceed antioxidant capacity oxidative damage is caused.
- Chronic disease and metabolic disorders are likely a result of the collapse in this system.
Programming cell death
- Mitochondria detect defects and damages in cells.
- Upon discovering cell weaknesses, mitochondria initiate programmed cell death called apoptosis.
- If the mitochondria are not functioning correctly, this initiation process might go haywire, and if this happens, damaged cells can remain in the body.
- Damaged cells may lead to inflammatory conditions, autoimmune disease, cancers, etc.
Mitochondrial Fusion & Fission
- Mitochondrial health is dependent on the balance of two mitochondrial processes known as fusion and fission.
- When cells experience metabolic or environmental stresses, mitochondrial fusion and fission work to maintain functional mitochondria.
- These simultaneous and continuous procedures are crucial for maintaining optimal mitochondrial activity in response to its ever-changing environments.
- The shapes of mitochondria in cells are continually changing via a combination of fission, fusion, and motility.
- Both fission and fusion are heavily reliant on several specialised proteins to perform their functions competently.
- Breakdowns in this process may lead to an imbalance in the body, causing damage to vital organs.
Fusion
- Two mitochondria fusing can help repair any DNA damage that might be present in the mitochondria, to bring back functionality.
- An increase in fusion activity leads to mitochondrial elongation.
- Fusion assists in modifying stress by integrating the contents of slightly damaged mitochondria allowing two mitochondrial genomes with different defects to encode what the other lacks and thereby generate all of the necessary components for a functional mitochondrion.
- Defects in the fusion of mitochondria are associated with neurodegenerative diseases such as Parkinson’s disease.
Fission (division)
- A mitochondrion divides into two or more structures.
- An increase in fission activity results in mitochondrial fragmentation.
- It plays a role in eradicating unstable mitochondria from the body through the programmed cell death process known as apoptosis.
Mitochondria & Free Radicals
- Free radicals are by-products of the energy production cycle.
- Referred to as ROS-reactive oxygen species.
- ROS are highly reactive unstable molecules.
- Antioxidants stabilise and neutralise ROS.
- Oxidative stress is the condition when there are more ROS than antioxidants.
- Oxidative stress can damage DNA, impair the use of fats and proteins, and create mitochondria dysfunction which will starve the cell of the energy it needs.
- If energy requirements are not fulfilled the cells either becomes defective or die.
- Oxidative stress causes the release of more ROS in an ongoing vicious cycle leading to long term health issues.
- Mitochondrial DNA does not have the same protective armour as regular DNA found in the cell nucleus – so it is more susceptible to ROS damage.
- But ROS are not all bad – they are also essential messaging molecules sending messages between cells to regulate immune cells and assist the body in cleaning out damaged cells, etc.
- Maintaining a basal level of ROS in cells is essential for life.
- More research is needed to understand how and when ROS become useful.
Causes of mitochondrial dysfunction
Inherited
- Genetic mutation
- in mitochondrial DNA (mtDNA)
- in nuclear genes that code for mitochondrial components.
Acquired
- adverse effects of drugs – pharmaceutical and or recreational
- infections
- excess damage due to the imbalance between ROS and antioxidant levels caused by:
- oxalates in foods
- cigarette smoke
- industrial chemicals
- air pollution
- X-rays
- other environmental factors
Mitochondrial dysfunction signs and symptom
Because mitochondria are present in 90% of cells symptoms will depend on which cells and or organs are affected.
The most affected systems are the brain, heart, liver, skeletal muscles, kidney, endocrine and respiratory systems.
Possible symptoms
BRAIN
- Developmental delays
- Mental retardation,
- Seizures
- Dementia
- Parkinsons
NERVES
- Weakness
- Pain
MUSCLES
- Weakness
- Cramping
- Pain
HEART DISEASE
- Extreme fatigue
- Upper body discomfort
- Dizziness
- Shortness of breath.
EYES
- Twitching
- Vision loss
KIDNEY DISEASE
- Foamy urine
- Puffiness around the eyes
- Frequent urination
RESPIRATORY PROBLEMS
- Low O2 saturation
- Colour changes
- Noisy breathing
- Cold and clammy skin
HEARING LOSS
- Reduced ability to hear other people, TV, phone etc.
GASTROINTESTINAL DISORDERS
- Difficulty swallowing
- Constipation
- Bloating
LIVER DISEASE
- Jaundice
- Legs and ankles swelling
- Pain on the right side just under the ribs
DIABETES
- Increased thirst
- Frequent urination
- Slow healing cuts and wounds
LACTIC ACIDOSIS
- Muscle ache
- Rapid breathing
- Nausea
INCREASE IN INFECTIONS
- Impaired immune function.
Testing mitochondrial dysfunction
Establishing metabolic dysfunction isn’t easy as symptoms can be extensive and diffuse due to which cells and organs are involved
Metabolic dysfunction is generally considered the cause when 3 or more organ systems are involved
- Genetic testing
– testing both mitochondrial and nuclear DNA - Urine, blood and spinal fluid testing
– Urine tests - Muscle biopsy
– examines the mitochondria and tests enzyme levels. - MRI – Magnetic resonance imaging
– of the brain and spine - Breath testing
– the level of CO2 in the breath gives an indication of which nutrient is being ‘burnt’ glucose or fats - OCR – Measurement of the oxygen consumption rate
– which is the current testing of choice to determine underlying mitochondrial dysfunction. Using oligomycin to reduce mitochondrial O2 consumption and blocks ATP production then measuring any O2 not consumed - GKIC – Glucose ketone index calculator
– looks at your glucose to ketone ratio. Ketones must be measured by blood, not urine. Glucose must be measured in mmol/L not in mg/dL. A glucose ratio of 2.0 or below is a healthy zone. - Mitochondrial NAD(P)H – A decrease in mitochondrial NAD(P)H can indicate enhanced electron chain activity and an increased NADH oxidation, reduced Krebs cycle activity with a decreased NAD+ reduction, or increased NAD+ consumption.
- See article for more detailed information about the various tests.
What screws up the mitochondria
- Genetics
– Mutations in mitochondrial DNA (mtDNA)
– Mutations in nuclear genes that code for mitochondrial components.
- Chemicals
- Toxins
- Pesticides
- Herbicides
- Mycotoxins and molds
- Viral infections like EBV, HIV, COVID
- Parasites
- Heavy Metals
- Certain medications, such as antibiotics
- Chronic inflammation
- Chronic oxidative stress
- Alcohol
- Excess copper
- Lack of antioxidants
- Lack of oxygen
- Lack of iron
- Lack of glucose and fats
- Lack of B-vitamins
- Oxalates in the diet – Leafy greens like spinach, Rhubarb, Soy Products, Almonds, Potatoes, Beets, Navy Beans, Raspberries
- Lack of sleep
- Chronic stress
- Excess glucose
- Excess Omega 6 fatty acids
- Excess endurance exercise.
Minding & Mending Mitochondria
- Mitochondria rely on a vast supply of nutrients to work effectively.
- They are dependent the body to provide the right fuel to perform their tasks.
Nutrients that aid mitochondrial function
- Co-Q10
- Quercetin
- Resveratrol
- L-carnitine
- N-acetyl cysteine
- Glutathione
- Vitamin C
- Selenium
- B vitamins
- Niacinamide (B3)
- Magnesium
- Zinc
- Manganese
- Iron
- Sulforaphane
- Alpha lipoic acid
- Omega 3 fatty acids
- Vitamin E
- Intravenous ozone
Activities that aid mitochondrial function
- Use the principles of hormesis to increase mitochondrial function – see the article in this blog and the following examples
- Time-restricted eating (TRE) – improves your mitochondrial health and metabolic flexibility
TRE is a form of intermittent fasting in which you restrict all of your food intake to a certain number of consecutive hours each day.
Keeping your eating to a window of six to eight hours a day is an achievable goal for most people
Metabolic in-flexibility is probably the underlying problem in the vast majority of diseases. Read my article about a fast way to healthy, beautiful aging. See link below.
Lower your intake of carbs aka glucose – high carbs supress fat utilisation
Higher your fat intake, especially short and medium chained fatty acids
Test your breath to see if you burn glucose or fat – glucose, produces more CO2
- Hypoxia / low oxygen concentrations – lead to improved ATP production and reduced ROS generation
- Cold exposure – such as finishing your shower with 30-60 seconds cold water
- Ozone therapy
- H:I:T exercise – such as 2 x 30-second-intervals of all-out, max exertion:
– 30 seconds
– 4 – 5 minutes of rest
– 30 seconds
– 3 times a week.
- Decrease stress
- Detox heavy metals
- Red and NIR / near infrared light therapy – increase melatonin production a very powerful antioxidant that mops up free radicals in the mitochondria. Melatonin also helps increase glutathione, the body’s major detoxification agent.
- Address any thyroid issues.
Hormesis Theory
- Within the fields of biology and medicine hormesis is defined as an adaptive response of cells and organisms to a moderate (usually intermittent) stress.
- So things that will be negative if exaggerated can be good in small doses
- What doesn’t kill you makes you stronger..
Examples include
– H:I:T exercise
– TRE – intermittent fasting
– Exposure to extreme temperature changes
– Hypoxia
– Exposures to low doses of certain phytochemicals, such as sulforaphane and resveratrol
– Sulforaphane
Ozone therapy
- Nothing to with ozone in the atmosphere.
- It’s pure oxygen – 3 oxygen atoms combined together which are electron deficient.
- Regular oxygen that we breathe is what we call O2 – 2 oxygen atoms combined together.
- Ozone put into the human body, starts grabbing electrons forming peroxides which are ROS-reactive oxygen species.
- After ozone treatment, the body is loaded with peroxides, which can stay in the body for a good 7 – 14 days.
- Ozone works as a hormetic molecule, working as a pro-oxidant to increase the body’s antioxidant response.
- At lower doses this can be beneficial but as ozone increases it does the exact opposite.
- So, deciding on the dose for ozone is pretty critical.
- To stimulate mitochondrial function doses of 10, -12 mg intravenously through a machine that converts pure medical grade oxygen to pure ozone.
Mitochondria & Steroid hormones
- Steroid hormones are a chain of hormones made from cholesterol in the mitochondria and endoplasmic reticulum.
- It all starts with cholesterol being transported into the mitochondrial, which is the limiting factor in the production of the steroid hormones.
- Cholesterol converts to pregnenolone which exits the mitochondria to the endoplasmic reticulum where it converts to progesterone, androgens and estrogens.
- Pregnenolone is also transported back to the matrix where it converts to cortisol and aldosterone.
Mitochondria Estrogen & Sirtuin
- Mitochondria are important producers of estrogen biosynthesis and are also targets for estrogen action.
- Aging in women is associated with a reduction in estrogen formation and the development of mitochondrial dysfunction.
- Sirtuin proteins are considered to be longevity proteins.
- Sirtuin proteins, SIRT3, SIRT4 and SIRT5, are located in mitochondria matrix and have been implicated in regulating metabolic processes.
- Sirtuin 3 (SIRT3) and estrogen may work together to rescue mitochondrial activity in aging by increasing antioxidant defence activity.
- High levels of SIRT3 increases respiration and decreases the production of ROS reactive oxygen species.
- Fasting increases SIRT3 expression as does resveratrol.
Mitochondria & Thyroid
- Your thyroid may also need to be addressed if your mitochondrial function is impaired.
- Suboptimal thyroid function is common over the age of 50
- Resting metabolic rate – how much energy your cells are producing when you’re resting is almost entirely determined by Thyroid hormone.
- Thyroid hormone also activates something called uncoupling protein 3 (UCP3), important for ATP production.
- Thyroid also stimulates mitochondrial biogenesis, and stimulates mitochondrial fission/division, so when the cells divide, you get cells with the same number of mitochondria.
- Thyroid is very important for fatty acid metabolism of mitochondria.
- If your Thyroid needs supporting using bioidentical thyroid hormones from desiccated animal thyroid which contain all 4 thyroid hormones – T1, T2, T3 and T4 or at the very least T3 and T4, in particular T3.
- TSH testing may not provide an accurate picture, resting metabolic rate may be a better way of doing this, such as measuring morning body temperature
- Normal functioning thyroid – 36.5C – 36.7 C
- Low/hypothyroid – constantly under 36.5 C
- High/hyperthyroid – constantly over 36.7C
- Blood testing for Thyroid function should include both thyroid hormones – Free T4 and Free T3
Do your own testing.
Energy & Aging
- Aging is not the same as getting older.
- It is the progressive physical and mental deterioration that occurs as we get older.
- In fact every aspect of physiology, such as the ability to heal, the ability to move, the ability to think, etc., is 100% dependent on energy production.
- Aging is inevitable, the rate and extent of aging is solely dependent on the body’s ability to produce energy.
- Decreased energy production is the cause of aging, not the result of it.
- By maintaining youthful energy production, you can slow body aging.
- Lifestyle choices can increase or decrease energy production.
Questions? Please don't hesitate to contact me
