Mitochondria Aren't Just the Powerhouse of the Cell

I'm going to make a bold prediction. You could watch this video 5 seconds after it's posted and someone will already have commented that mitochondria is the powerhouse of the cell. It's pretty clear how these little organelles became a meme. It's gotta 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. Side note, 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 jelly bean 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 jelly bean 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 to 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 more in 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 600 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 that 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 cells, 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 cells' 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 only a small circle with about 16,000 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 200,000 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 systems 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 this 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, we'll prevent that immune response within the cell and find more effective chemo treatments. 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 going to try to teach you all how ATP works without making you fall asleep from boredom. Wish me luck. I'm Patrick Kelley, thanks for watching this episode of Seeker Human.