and someone will already have commented the mitochondria is the powerhouse of the cell.

It's pretty clear how these little organelles became a meme. It's got to be the most repeated

line in biology and has been firmly inserted into our middle school textbooks for years.

There's just something catchy to it. Sidenote, do powerhouses say they're the mitochondria

of wherever? If you're in charge of the PR for a powerhouse anywhere in the world,

DM us.  That whole powerhouse nickname came from the mitochondria's energy production

capabilities, but it's so much more than that. Today we'll go over how this little

powerhouse powers our cells, where it came from, and some new research that you probably

didn't hear about back in your middle school textbook.

You may remember some variation

of this diagram, a classic animal cell with a little jellybean-shaped organelle called

the mitochondrion. Mitochondrion for singular, mitochondria for plural. That diagram is fine

when you're learning the structures for the first time, but of course, a real life

cell is more complex. That little jellybean shape is only one of the possible shapes a

mitochondrion can take. What it looks like can be different from cell to cell. Plus,

you don't just have a handful of mitochondria per cell, you have hundreds to thousands of

them floating in your cells. And even that number depends on what type of tissue we're

talking about. Like a skeletal muscle cell might be 3 to 8 percent mitochondria by volume

but a liver cell could be about 20 percent. Meanwhile, heart muscle cells are laughing

at those numbers because they're about 35 - 40 percent mitochondria by volume. They

win by a long shot. Now, all mitochondria do have some structural things in common. They

each have two membranes — one outer layer, one inner layer, and some space in between

them.That outer membrane works like a protective but permeable layer, letting different compounds

in or out of the mitochondrion. Meanwhile the inner membrane is where some important

biology happens to manufacture ATP. This is the molecule that fuels our major biological

processes, so it's often called energy currency. We're going to get into more depth on that

whole ATP thing in the next video, but this inner layer, as well as the matrix within

the mitochondria, is where the cells generate most of their ATP. Zooming back out to the

mitochondrion as a whole, it looks almost like a separate cell in its own right. That's

because at one point, it was. The most widely accepted theory of how we got these little

guys is the endosymbiosis theory. Endo- meaning into, -symbiosis meaning living together — this

word means that one cell engulfed another cell and it resulted in a mutually beneficial

relationship. About 3.8 billion years ago, earth's atmosphere didn't have oxygen

in it, and the only things living on our planet were single celled organisms that were anaerobic,

meaning they didn't need oxygen to survive. Fast forward about six hundred million years and

photosynthetic bacteria were everywhere, taking sunlight and a few other ingredients and cranking

out oxygen as a byproduct. A few hundred million years later, those photosynthetic bacteria

had produced so much oxygen that it fundamentally changed the composition of Earth's atmosphere. Here's

the thing, oxygen was actually toxic to those anaerobic cells. It's so bizarre that something we

need on a daily basis was so deadly back then. It's like if I found out my ancestors were allergic

to tacos. That meant that these anaerobic bacteria were at a huge disadvantage once

the atmosphere was made of, what was to them, poison gas. By two and a half billion years

ago, a new type of bacteria started showing up in the fossil record. These bacteria were

aerobic, meaning they could use oxygen, and it even helped them create energy. That is

an excellent evolutionary advantage when the atmosphere is made of a gas you can use. The

theory suggests that eventually, one of those anaerobic single celled organisms consumed

an aerobic purple bacteria that survived being eaten and they kicked off a symbiotic relationship.

That was the first mitochondria. That purple bacteria could consume and metabolize oxygen,

which provided energy for the host cell. And in return, the host cell protected the bacteria.

We still don't totally know the conditions around that moment of symbiosis, but we have

fossil evidence of it starting about one and a half billion years ago. The result of this

ancient endosymbiosis is today's powerhouse of the cell. We kept mitochondria around to

make energy for our cells. And since they were once their own separate organisms, they

retained certain features of their past selves, one of which was their genetic information.

Just like our larger cells, mitochondria need certain proteins to do their jobs, so they

need genes to tell them what proteins to make. Our DNA, which makes up our genes, is kept in

our cell's nucleus, what I'll call nuclear DNA for the rest of the episode. Some of our

nuclear DNA makes proteins for the mitochondria, then ships them out for it to use. But the

mitochondria also has its own DNA, separate from the DNA in your cell's nucleus. Plus,

it has the cellular machinery to make new mitochondrial proteins, again, separate from

the rest of your cell. This is the mitochondrial genome, or the entirety of its genetic information,

and it's much smaller than the genome in the cell's nucleus. It's a small circle

with only about sixteen thousand base pairs while the nuclear genome has billions of

base pairs. Now, the vast majority of proteins that get used by the mitochondria come from

nuclear DNA, but that mitochondrial DNA lets us make some cool observations. Thanks to

sexual reproduction, humans are genetic mishmashes of our parents, so you might expect that our

mitochondrial DNA comes from our parents too. As a matter of fact, for a few reasons, we only

inherit mitochondrial DNA from our mothers. When you were first developing in utero, most

of the chromosomes from your biological parents recombined to form your chromosomes. This

is part of what makes you physically different than your parents. But mitochondrial DNA,

as well as the Y chromosome from your father, don't recombine so they get used to study

lineage. This kind of DNA does mutate, but it's otherwise well conserved, so the information

in our mitochondria's genes are similar to our maternal ancestors way way back in

the past. Sequencing that mitochondrial DNA and comparing genomes has allowed researchers

to trace people back to a single female ancestor in Africa thousands of years ago, and follow

human migration. Now, why does mitochondrial DNA only come from your mother? Good question!

The first is that egg cells hold way more mitochondrial DNA than sperm cells, it's

around two hundred thousand molecules in an egg cell and like, single digits, in sperm

cells. Some estimates are a little higher, but the point remains — egg cells outnumber

sperm by a lot when it comes to mitochondrial DNA. Plus, sperm store most of their mitochondria

in their metabolically active tails. It does take a lot of energy to swim, after all. Now,

aside from helping your cells make energy and providing clues about our ancestry, ongoing

research is showing us some new features of our mitochondria. For example, research by

scientists at the Salk Institute showed that mitochondria can kick off a series of events

that signal the rest of the cell that it's under stress — the kind of chemical stress

that can damage DNA. This phenomenon caught their attention when they observed how defective

mitochondrial DNA caused the cell to eject the damaged mitochondria and actually send

out a chemical warning signal that strengthens the cell's defenses. So they investigated

what would happen if any of that DNA spilled out of the mitochondria and into the liquid

around it. When they did, they saw that a certain set of genes were activated that usually activate

when there's an invading virus. Awesome, that's exactly what we want our immune system to

do, attack a virus when it detects one. Now, that same set of genes is also activated by

chemotherapy-resistant cancer cells. Specifically, cancer that's resistant to doxorubicin,

a chemotherapy drug that attacks nuclear DNA. When they studied this drug more closely,

they found that it caused the release of mitochondrial DNA from the mitochondria, which activated

a subset of those protective genes, which then protected the nuclear DNA. The point

of this drug was to attack nuclear DNA, but when these genes were activated, it set up

a pathway to defend the nuclear DNA, which explains why some cancers were resistant to

the drug. The researchers took cancer cells and induced stress on their mitochondrial

DNA, and as expected, they activated more of those genes and developed a resistance

to doxorubicin afterwards. This research doesn't show that doxorubicin is a useless

chemotherapy drug, it just explains why some cancers develop resistance to the drug. They

think the purpose of that response is to protect the DNA in the cell's nucleus, making the

mitochondria a warning signal that something bad is happening. They hope that if they

can find a way to protect the mitochondrial DNA, they'll prevent that immune response

within the cell and find more effective chemo treatments. So not only is our powerhouse

of the cell effective in generating energy, it's got a fascinating backstory, with clues

to our past and to our future medical treatments. If you're wondering why we kind of glossed

over the energy generating aspects of the mitochondria, it's because we're saving

it for later. Check out the next episode in the series to learn about how our cells generate

energy. Yep, I'm gonna try to teach ya'll how ATP works without making you fall asleep

from boredom. Wish me luck.

I'm Patrick Kelly, thanks for watching this episode of Seeker Human.