How Mitochondria Dysfunction causes Disease [Science Explained]

Summary

This script delves into the vital role of mitochondria in cellular energy production and their intricate connection to various diseases. Highlighting the mitochondria as a central hub for metabolic health, the discussion explores their function in energy transformation and how dysfunction can lead to health issues like insulin resistance and obesity. The video also touches on the historical focus on the endoplasmic reticulum and questions whether the current mitochondria-centric view might be overlooking other cellular components.

Takeaways

• 🔬 Mitochondria are often referred to as the 'PowerHouse of the cell' due to their role in energy production.
• 📚 The speaker has extensive experience with mitochondria, having published multiple papers and reviews on the topic.
• 💡 Mitochondrial dysfunction has been linked to a wide range of diseases, indicating their importance in overall health.
• 🧬 Despite the lack of direct blood tests for mitochondria, their function and dysfunction significantly impact health at a cellular level.
• 🚫 Mitochondria are not essential for cell survival, as cells can generate energy through alternative pathways like anaerobic glycolysis.
• 🔋 Mitochondria are highly efficient in energy production, primarily using fats and generating more ATP per molecule compared to other pathways.
• 🧠 The brain is a prime example of the importance of energy for consciousness; without blood flow, and thus energy supply to the brain, consciousness is lost.
• 🔄 Mitochondria rely on nutrient molecules and oxygen to generate ATP through a process involving the electron transport chain.
• 🚨 Metabolic dysfunction, including insulin resistance, can be seen as impaired energy flow and has systemic effects on health.
• 🍽️ Overnutrition can lead to an oversupply of electrons to mitochondria, resulting in the production of free radicals and potential cellular damage.
• 🔍 The scientific community's focus on mitochondria in disease is reminiscent of past focus on the endoplasmic reticulum, suggesting a need for balanced research perspectives.

Q & A

What is the primary function of mitochondria in the cell?

Mitochondria are often referred to as the 'powerhouse of the cell' because their primary function is to generate energy in the form of adenosine triphosphate (ATP) through a process called cellular respiration.

Why is it challenging for people to understand the importance of mitochondrial function in health?

It is challenging because mitochondria are not typically measured in standard blood tests, and their dysfunction is not directly observable, making it a leap for some to understand their widespread impact on health.

What is the role of the electron transport chain in mitochondria?

The electron transport chain is a series of proteins within the mitochondria that use the input of molecules from food to transfer electrons and, with the help of oxygen, generate ATP, the cell's energy currency.

How does the lack of blood flow to the brain affect mitochondria and consciousness?

If blood flow to the brain is impeded, mitochondria cannot receive the necessary nutrient molecules and oxygen, leading to a rapid halt in ATP production. This lack of energy supply causes consciousness to disappear as the brain cells are no longer being nourished.

What is the connection between mitochondrial function and metabolic health?

Mitochondrial function is central to metabolic health because they are responsible for energy transformation. Any impairment in mitochondrial function can lead to metabolic dysfunction, which may manifest as insulin resistance, obesity, or other related conditions.

How do mitochondria generate ATP more efficiently than other cellular processes?

Mitochondria generate ATP more efficiently because they primarily use fat molecules for energy and produce a higher yield of ATP per molecule compared to other non-mitochrondrial energy generation pathways.

What is the impact of overnutrition on mitochondrial function?

Overnutrition can lead to an overabundance of nutrient molecules being delivered to the mitochondria. If the demand for ATP is not high, such as during inactivity, this can result in electron slippage, the formation of free radicals, and eventually cellular damage or dysfunction, including insulin resistance.

What was the scientific focus on cellular components before the mitochondria-centric view became prevalent?

Before the mitochondria-centric view, the scientific community was particularly focused on the endoplasmic reticulum, linking its dysfunction to multiple diseases.

How does the video script differentiate between the role of mitochondria and the endoplasmic reticulum in cellular health?

The script suggests that while the endoplasmic reticulum's issues still matter, they do not provide the whole answer to cellular health. Mitochondria, on the other hand, are positioned to have a greater control over cellular health due to their central role in energy production.

What is the significance of the conversation between the speaker and their principal investigator (PI) in the script?

The conversation highlights the historical context of scientific focus within cellular biology, cautioning against viewing mitochondria as the sole answer to all cellular health issues, and emphasizing the importance of a holistic understanding of cell function.

What is the potential 'surprise' mentioned at the end of the script that the speaker had in a conversation with a researcher?

The script does not provide specific details about the surprise, but it suggests that there will be a revelation or an insight in a subsequent video that challenges or expands upon the current understanding of mitochondrial function in health and disease.

Outlines

00:00

🔬 Mitochondria: The Cellular Powerhouse and Its Role in Health

This paragraph introduces the concept of mitochondria as the 'PowerHouse' of the cell and acknowledges the speaker's extensive experience with mitochondria in the lab. It discusses the role of mitochondria in disease, referencing a paper on mitochondrial dysfunction and its mechanisms. The speaker aims to use an interview format to explore the connection between mitochondria and various diseases, highlighting the difficulty of measuring mitochondrial health directly through blood tests. The paragraph emphasizes the widespread impact of mitochondrial function on health and the importance of understanding this connection for disease prevention and treatment.

05:01

💡 Energy Generation and Mitochondrial Efficiency

The second paragraph delves into the role of mitochondria in energy generation, particularly the production of adenosine triphosphate (ATP). It clarifies a common misconception that cells require mitochondria for energy, explaining that while cells can generate energy through other pathways like anaerobic glycolysis, most rely on mitochondria due to its higher efficiency. The paragraph also emphasizes the importance of nutrients and oxygen for the electron transport chain within mitochondria, which is crucial for ATP production. It provides a real-world example of how the lack of blood flow to the brain can quickly lead to the death of brain cells due to the cessation of mitochondrial function, illustrating the critical role of energy in sustaining life and consciousness.

10:02

🌐 Metabolic Dysfunction and Its Impact on Mitochondrial Health

In this paragraph, the discussion shifts to the broader implications of metabolic dysfunction and its impact on mitochondrial health. It touches on the concept of metabolic syndrome, which encompasses a range of diseases including obesity and diabetes, and how these conditions can affect mitochondrial function at various levels of biological complexity. The paragraph explains how overnutrition can lead to an overabundance of nutrient molecules, causing a phenomenon known as 'electron slippage' within mitochondria, which in turn generates free radicals and leads to cellular damage and insulin resistance. The speaker also reflects on the historical focus on the endoplasmic reticulum in disease studies, suggesting that while mitochondria may be a central player, it is important to consider the whole cellular context.

Keywords

💡Mitochondria

Mitochondria are organelles found in the cells of eukaryotic organisms, known as the 'powerhouse of the cell' due to their role in generating adenosine triphosphate (ATP), the cell's primary source of energy. In the video, mitochondria are discussed as central to cellular function and implicated in a wide range of diseases, highlighting their importance in health and disease processes.

💡Mitochondrial dysfunction

Mitochondrial dysfunction refers to the impaired ability of mitochondria to perform their normal functions, particularly in energy production. The script mentions a paper on this topic, emphasizing that alterations in mitochondrial function are linked to various diseases, suggesting a broad impact on health.

💡Electron transport chain

The electron transport chain (ETC) is a series of protein complexes found in the inner mitochondrial membrane that plays a crucial role in the production of ATP through oxidative phosphorylation. The script describes how the ETC requires nutrient molecules and oxygen to generate ATP, illustrating the process by which mitochondria produce cellular energy.

💡ATP (Adenosine triphosphate)

ATP is the primary energy currency of the cell, used to power various cellular processes. The video script explains that mitochondria are responsible for producing ATP through a highly efficient process compared to other energy generation pathways, emphasizing the high yield of ATP per molecule of nutrient.

💡Aerobic vs. anaerobic glycolysis

Aerobic glycolysis is the process of glucose breakdown to produce ATP in the presence of oxygen, while anaerobic glycolysis occurs without oxygen. The script points out that cells can generate energy through mitochondria-independent pathways like anaerobic glycolysis, but most cells rely on mitochondria for a more efficient energy yield.

💡Metabolic dysfunction

Metabolic dysfunction is a broad term that encompasses various disorders related to the body's energy metabolism. The script discusses how impaired energy flow, including insulin resistance and obesity, can reflect metabolic dysfunction and impact mitochondrial function, which in turn affects overall health.

💡Insulin resistance

Insulin resistance is a condition where cells do not respond properly to the hormone insulin, leading to higher blood sugar levels. The video script connects insulin resistance to metabolic dysfunction and its impact on mitochondrial function, suggesting a role in the development of metabolic syndrome.

💡Electron slippage

Electron slippage is a phenomenon where electrons not properly utilized in the ETC can interact with other molecules, forming free radicals. The script describes how overnutrition can lead to an over-delivery of electrons, causing electron slippage and the production of free radicals, which can damage cells and contribute to diseases.

💡Free radicals

Free radicals are unstable molecules with unpaired electrons that can cause damage to cells by reacting with other cellular components. The video script explains that free radicals generated by electron slippage in mitochondria can lead to cellular damage and dysfunction over time.

💡Metabolic syndrome

Metabolic syndrome is a cluster of conditions, including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol levels, that increase the risk of heart disease, stroke, and type 2 diabetes. The script discusses how mitochondrial dysfunction may contribute to the development of metabolic syndrome.

💡Endoplasmic reticulum

The endoplasmic reticulum (ER) is a cellular organelle involved in protein synthesis and other functions. The script mentions a historical focus on the ER's role in diseases, suggesting a comparison to the current emphasis on mitochondria, and raises the question of whether the focus on mitochondria is a repetition of past scientific trends.

Highlights

Mitochondria are often referred to as the 'PowerHouse of the cell' due to their role in energy production.

The lab has published multiple papers and reviews on mitochondria, including one on mitochondrial dysfunction and its mechanisms.

Mitochondrial function and dysfunction can impact health, though they are not directly measurable through standard blood tests.

Almost any disease can have a scientific study linking it to mitochondrial impairment.

Mitochondria are vital for energy generation, although cells can generate energy through mitochondria-independent pathways.

Mitochondria are more efficient at energy production, primarily using fats and generating more ATP per molecule.

The importance of energy for human life and consciousness is exemplified by the rapid loss of consciousness when blood flow to the brain is blocked.

Mitochondria require nutrient molecules and oxygen to generate ATP through the electron transport chain.

Interruption of blood flow, such as during a stroke, can halt mitochondrial function and lead to cell death.

Metabolic dysfunction reflects impaired energy flow and can manifest as insulin resistance and obesity.

Metabolic dysfunction at the cellular level can affect the whole organism's function, with mitochondria playing a central role.

Overnutrition can lead to an overabundance of nutrient molecules, causing electron slippage and the production of free radicals.

Free radicals generated by mitochondria due to overnutrition can cause cellular damage and contribute to diseases like insulin resistance.

The connection between mitochondria and disease has become a central focus in recent years, similar to past focus on the endoplasmic reticulum.

Improving mitochondrial health is a key area of interest, with potential implications for managing various diseases.

The conversation suggests a need for a balanced view on the role of mitochondria in health and disease, avoiding oversimplification.

Transcripts

it's the PowerHouse of the cell let's go

ahead and get that out of the way

because I know it's coming that said

I've released a good amount of content

on mitochondria in the past because I

have a wealth of experience working with

mitochondria in the lab our lab has

published multiple papers and reviews on

mitochondria including one paper on

mitochondrial dysfunction specifically

the mechanisms I may touch on that a bit

here but what I'd like to do is use a

video wherein The Host interviews a

mitochondrial researcher and asks about

the role mitochondria have in disease

and as they discuss it I'll add in some

of the details and take you into

yourselves also at the end I have

something to say based on a conversation

that I had with a researcher that might

surprise you but we'll wait on that for

now let's listen to Dr Picard no not

Captain Picard Dr Picard yeah like how

you said if you look at it from a mitoc

Centric standpoint like coming from like

the M mitochondria as the center but I

think that's a hard thing for a lot of

people to do because you can't see

mitochondria you can't you know you

don't get a blood test for mitochondria

right you get a blood test for your

hemoglobin levels and your your kidney

function and your liver function but you

don't you don't measure mitochondria so

um it's sort of like a leap for people

to say or for some people to understand

how widespread mitochondrial function

and dysfunction impact our health but is

it safe to say that they're kind of

involved with I mean just about any

health or or disease process at its core

could be related to mitochondrial

function yes uh certainly we try to you

know review this um and I should you

know take a step back and say we think

of mitochondria and you know that

organel as as you know a potential cause

first a a source a source of health and

and and life then a cause of potential

diseases that's a scientific model right

it's a hypothesis that we're you know

invested in in rigorously testing and

um so we need to you know do this

carefully but what the evidence that's

there if you go into pbet or into Google

and you look for studies that have

looked at some mitochondrial impairment

mitochondrial have many functions right

so alterations and some mitochondrial

function including energy transformation

but also mitochondrial signaling and any

disease you can think of there is likely

a scientific study that has investigated

and identified you know a connection a

few good points here one it's true that

when we look to measures of our health

we typically rely on blood measures

which are famously devoid of

mitochondria because red blood cells do

not contain mitochondria additionally we

look to peptides like hormones and

saccharide molecules like glucose and

many other intercellular molecules that

allow us to measure the health of our

cells our body through the communication

between cells but not nearly as much as

focused on within our cells known as

intracellular they're tightly linked but

intercellular will tell us little about

mitochondrial Health directly so why do

we care about mitochondrial Health as Dr

peard mentioned you can look up almost

any disease and find a link to

mitochondria as you can see there's an

abundance but that's just a tiny sample

and then the question is are impairments

and mitochondrial biology driving those

diseases and I think the answer is

likely yes real quick this is the point

that I'm going to return to later but

it's not quite as cut and dry as he's

positioning it here but I digress let's

listen uh and and why is that I think

it's likely because energy is such a

central part of of what we are and you

know of who we are to to some extent um

so I think that's why you know Mond have

been implicated and are you know there's

growing interest in in understanding the

connection between mitochondrial biology

and and health and and different

disorders is because energy is is

Central to to what we are and you know

how function and Captain peard I mean Dr

peard mentioned that mitochondria are

vital for energy generation technically

that's not true but I'm getting

extremely technical here so I'll go

ahead and say that I agree with them you

see your cells don't require

mitochondria they can generate energy

through mitochondria independent

Pathways such as a process called

anerobic

glycolysis but most cells rely heavily

on mitochondri because it's far more

efficient source of energy for a number

of reasons for one it uses fat molecules

for energy largely and two it generates

far more energy per molecule so the

yield is much higher most of your cells

energy is generated in the form of

adenosine triphosphate ATP and

mitochondria make multiple times more

ATP than our nonm mitochondrial energy

generation path so I'm nitpicking here

admit but that's why I agree but I

wanted to throw that in there for the

uninitiated if we think about the brain

if you want to convince yourself and

make this real because you're right we

can't see mitochondria and we have the

chance here you know to have cool

microscopes and you can put living cells

and make the mitochondrial fluorescent

and then you look down the eyepiece and

you see them move and like fuse and so

you you can see them if you have the

right equipment but our day-to-day

experience is you know is is that of you

know is our subjective experience and

the kind of the the reality of the body

and how we feed it and so on we're not

aware of our mitochondri which is

probably for the for the better but if

you want to convince yourself that how

Central Energy is if you just you know

block blood flow to the brain right if

you if you olude the blood going to you

you know perfusing your brain for just a

few seconds you're out Consciousness is

gone right and the reason Consciousness

disappears if you if you don't have

blood flow to your to your brain or if

your heart stops is because you're not

feeding your mitochondria anymore right

you're not bringing them oxygen you're

not bringing them food substrates and

that you know shuts down everything

right so mitochondria rely on two things

to generate ATP the cell energy that we

discussed and those two things are one

nutrient molecules like the ones that

you eat like sugar carbohydrates and

lipid fat and two they require oxygen

molecules if we zoom into your

mitochondria you'll see a chain of

proteins and this chain is called the

electron transport chain these five

proteins need an input of molecules that

were generated from your food molecules

that's the carbohydrates and fats that

we just discussed I'm not showing it but

these food molecules nutrients get

converted over and over into new

molecules that are eventually useful for

mitochondria once they've been converted

to their correct form they input energy

through a process called electron

transfer into the first protein of the

electron transport chain and at protein

4 we need oxygen to take up that

electron transfer in loose terms because

I'm skipping many steps in the electron

exchange this donation of electrons by

your processed food molecules to the

first protein and the eventual exchange

of that electron to oxygen allows your

mitochondria to generate generate ATP

cellular energy now imagine if blood

flow is impeded to the brain from

something like a hemorragic stroke or ES

schic stroke then neither the food

molecules nor the oxygen is being

delivered to the cell and therefore the

cell runs out of substrate to keep

mitochondria running this is more of an

issue in relation to oxygen because our

cells are capable of storing nutrients

but not capable of storing oxygen either

way mitochondria rapidly grind to a halt

ATP levels in the cells drop and the

reserves are consumed in seconds and

guess what happens to your brain

cells they die um so that's I think a

very real example of uh you know how

energy just sustains you know human life

and and and human consciousness uh so

anything we do as as you know you've uh

discussed uh you know with many

scientists and clinicians uh the way we

feed our body is the kind of energy we

put into the system can actually

influence right how the system works uh

the brain and and the whole organism

yeah so let's talk about that for a

second because you know one of the

things we focus on at metabolic mind is

the connection between metabolic and

mental health so when there's metabolic

dysfunction that can impact um mental

health and contribute to mental illness

and at its core presumably mitochondria

are involved in in that so how does

metabolic dysfunction and insulin

resistance and you know with some things

that are so prevalent in today's society

how does that impact

mitochondria so yeah metabolic

dysfunction is an umbrella term right

for that in in my view reflects um

impaired energy flow right so the what

sustains life is the you know blood flow

that you know the beating heart is like

a clear sign of life because by moving

blood you move energy you move oxygen

you move uh you know Ketone bodies and

fatty acids and and glucose and proteins

and so on so and these are energy forms

uh so

the disorders of of energy or metabolic

dysfunction can be reflected in insulin

resistance as which is reflected in or

which represents the inability of you

know cells to take in food substrates

when that's needed um so there can be

metabolic dysfunction at the whole

organism level right which can

um you know cause or materialize in

obesity for example then there's kind of

uh systems level metabolic dysfunction

insulin resistance would be a feature of

this at the cellular level there can be

you know metabolic dysfunction there and

then if we go inside the cell there can

be MIT cond uh energy transformation

defect or you know impairments which of

course ripples out if the mitochondria

are not functioning properly that can

impair how cells function how the tissue

function and how the whole organism

functions so mitochondri are kind of a

such a metabolic Hub that their their

their um inability to transform energy

properly or

misregulation of you know mitochondria

getting turned on and making a lot of

ADP or you know being dialed down and

making less ATP can really affect other

levels of of biological and

physiological complexity okay that was a

lot essentially they're discussing

metabolic syndrome which is a host of

different diseases lumped into one

connected Hub like obesity diabetes

cardiovascular disease and so on usually

they occur together in some capacity

although there are exceptions as one

example obesity or overnutrition can

cause mitochondrial subst those are the

nutrient molecules that deliver

electrons to the first protein and

technically they also deliver to the

second protein but I don't want to bog

this down so those nutrients are so

abundant and the need for ATP is not

high because the person isn't exercising

or being active so there's an overd

delivery of electrons and instead of

clearing them away by making ATP

mitochondria undergo electron slippage

which is exactly how it sounds they slip

on bananas and fall down the stairs

no they literally slip off the proteins

that are supposed to hold on to them and

they interact with molecules they're not

supposed to interact with which

generates unstable molecules called free

radicals these free radicals then cause

damage to components of the cell as they

interact if this occurs over years the

cell is continuously being assaulted

internally and more and more damage

occurs until the cell dies or becomes

dysfunctional one One symptom being

insulin

resistance again there's a lot more here

and the mechanisms between insulin

resistance and cardiovascular disease in

mitochondria take on several different

flavors but I hope that you have a

better understanding of how obesity or

overnutrition causes harm

intracellularly so far there's been a

lot of talk about mitochondria and funny

enough when Dr Picard says this and then

the question is are impairments and M

cob biology driving those diseases and I

think the answer is likely yes it

reminded me of a conversation that I had

with my Pi Pi is a term for principal

investigator he's the owner of our lab

we were discussing how mitochondria

Centric everything has gotten in

relation to disease like I showed you

earlier there are so many different

studies that look at the connection

between mitochondria and disease but he

mentioned to me that just 20 or 30 years

ago everyone was obsessed with the

endoplasmic reticulum which is another

section of the cell all these studies

were linking the ER to multiple diseases

so are we just repeating the same

mistake well I don't think so mainly

because the issues in the ER still

matter but they just don't happen to be

the whole answer just like I'm not

necessarily going to jump on board with

mitochondria and say that it fixes every

issue although it is uniquely positioned

to have an even greater Gater control

over our cellular Health than even the

ER so the question is how do we improve

our mitochondria well for that my friend

let's take the Enterprise to the next

video linked right here for you or as

Captain Picard would say make it

so