BIOLOGY, ENERGY, AND EVOLUTION

CCBE — Part 6: Mitochondria, metabolism, and oxygen

How oxygen guided our coevolution with mitochondria and created our metabolism

Metabolism involves using energy to create molecules and tissue (anabolism), and destroying molecules to release energy for other uses (catabolism). This simplified diagram shows how catabolism breaks down larger molecules to repurpose their constituent materials and create some energy as ATP. The opposite occurs during anabolism, like when testosterone stimulates the growth of muscle cells (i.e., an ‘*anabolic’* steroid hormone). Source: Wikimedia Commons. Author: Tr4nv1v.

Recap

The birth of the eukaryotes was a turning point in biological history. Being able to rely on ATP from their mitochondria put eukaryotes in an enviable energetic position. This allowed them to overcome biophysical constraints that keep prokaryotes (bacteria and archaea) microscopic and almost exclusively unicellular to this day, as multicellularity, enormous size, and sex emerged among the eukaryotes.

Multicellular eukaryotes with specialised cells for reproduction, such as ourselves, are built on a foundation of cellular cooperation. Most cells live, work and die for the good of the collective without ever directly participating in reproduction, a basic goal of all living organisms. However, as we alluded to last time, these accomplishments in cooperation aren’t without their difficulties, and tensions remain between eukaryotes and their mitochondria.

Today

As we’ll see next time, this brings us to a type of molecule known as ‘free radicals’ and ultimately to the causes of cancer! However, in order to explain this tension and what it means for cooperation and competition, we first need to discuss the way mitochondria make ATP, which is our focus for today. This involves a process known as ‘cellular respiration’, an essential component of metabolism.

We’ll cover the relationship between cellular respiration and metabolism, how cellular respiration works, and the implications for biology and evolution. At the end, we’ll consider a wrinkle in our logic and see that it leads us directly to next week’s discussion of free radicals and the tension between eukaryotes and their mitochondria.

A short overview of metabolism

Cellular respiration is an essential part of metabolism, but isn’t the whole of metabolism. That’s because metabolism involves destroying molecules to release energy (catabolism) and using energy to build molecules (anabolism), as you can see in the diagram above. This is why steroid hormones that make you gain muscle mass, such as testosterone, are described as ‘anabolic’.

Cellular respiration is the ‘catabolic’ process in which molecules are destroyed to release energy. The energy released in cellular respiration (catabolism) also fuels the creation of larger molecules (anabolism), but the production of larger molecules is distinct from the process of cellular respiration. In this way, cellular respiration is a smaller circle within the larger circle of metabolism.

Catabolism also produces more than ATP, including the raw materials for making proteins (amino acids), DNA and RNA (nucleotides), and cell membranes (fats, usually referred to as lipids or fatty acids). We’ll return to this point in an upcoming article when we discuss current ideas about the genetic and metabolic factors behind cancer.

The hydroelectric dam metaphor of metabolism

Cellular respiration is the cell’s equivalent of breathing, and supporting this process is the reason why we breathe. It’s easy to get lost in the chemistry and molecular biology, and the details aren’t important for our purposes, so we’re going to tackle this with a metaphor and add relevant info on top.

The most commonly used metaphor is a hydroelectric dam. No metaphor’s perfect, but this one seems to be useful enough, even if it’s a bit clumsy at times. The idea is this. Inside all of our mitochondria, a reservoir acts like a small but powerful hydroelectric dam, generating energy as ATP. This works by filling the ‘dam’ to high capacity, the point of which is to build pressure against the dam wall.

There are turbines built into the dam wall, and this pressure forces those nanoscale protein-machines to spin, thereby producing energy in the form of ATP. The dam is filled by pumps that are powered by electricity (watch this video for details), except the scale is so small that the electrical current is literally individual electrons. It’s not easy to wrap your head around the scale of the nanoscopic world, but if you want to try, see the diagram below.

This diagram demonstrates the nanoscale, measured in nanometres. The diagonal lines highlight the scale of 1–100 nanometres, which is the conventional range that defines nanotechnology, such as those shown on the right. A nanometre is one billionth of a metre, meaning that there are 1 million nanometres in a millimetre. Glucose, near the top, is the primary sugar burned in aerobic respiration/metabolism. As you can see, it’s one tenth of a nanometre, meaning a line of 10 million glucose molecules would be 1 millimetre long. Burning glucose is especially important in brain cells, whose activity is more strictly dependent on the metabolism of glucose compared to other organs and tissues of the body. This is thought to be because brain cells need an energy source that enables rapid increases in activity, for which aerobic glucose metabolism is ideal. Source: Wikimedia Commons. Author: Sureshbup.

Cellular respiration comes in two flavours, one involving oxygen (aerobic), and the other involving stuff like sulfur and nitrate instead of oxygen (anaerobic). There’s also an alternative to respiration, known as fermentation.

Some eukaryotes (like yeasts) and prokaryotes (like certain bacteria) rely primarily on fermentation for generating energy. Most eukaryotes, including us, rely primarily on the oxygen-dependent (aerobic) type of respiration. This consumes oxygen and produces CO2 and water as waste, which are quite easily and safely dealt with by our bodies.

We can resort to fermentation when our cells are starved of oxygen, like in muscle fatigue. However, the accumulation of more harmful waste products, such as lactic acid, places a limit on how long fermentation can act as a substitute for aerobic respiration before we need to take a break. If we rely on fermentation for too long, like in an overly intense workout, the resulting build up of lactic acid (i.e., lactic acidosis) can even make us physically sick!

The lactic acid molecule. Source: Wikimedia Commons. Author: Jynto.

A very brief history of how oxygen on Earth drove the evolution of metabolism and life

When you look at chemical fingerprints in geological history, you find that oxygen took many billions of years to accumulate on Earth. For this reason, it’s believed that fermentation and the oxygen-independent (anaerobic) type of respiration evolved before oxygen-dependent (aerobic) respiration. However, as oxygen levels increased, organisms gradually adapted to the new normal, either embracing aerobic respiration or escaping to oxygen-poor nooks and crannies around the world.

We’re a good example of adaptation, as we embraced aerobic respiration and retained the ability to use fermentation if briefly starved of oxygen. Our gut bacteria are a good example of the escape strategy, as they thrive in the conditions of our stomach, which would ironically be a death sentence for ourselves. As this shift occurred, the eukaryotes dabbling in aerobic respiration stumbled on a major discovery: oxygen supercharges the efficiency of energy production.

This turn of events had dramatic consequences for the evolution of life on Earth. Compared to the alternatives, oxygen-dependent (aerobic) respiration increased the amount of ‘bioavailable’ energy that animals and plants could produce.

In turn, this extended the potential length of food chains, an increase in the ‘trophic levels’ of an ecosystem. This allowed populations to expand and diversify, and made predatory behaviour an energetically-viable lifestyle for many more organisms.

An atmospheric oxygen molecule (O2) is photolyzed (split into its two oxygen atoms) by a photon of the solar UV radiation (wavelength, say, 190 nm). Each of the two atoms (most likely) bind to other O3 molecules to form “hot” ozone molecules (O3), which have to be cooled by one or two collisions with (most likely) nitrogen (N2, not shown) to prevent immediate dissociation. However, the oxygen atom would try again. Eventually, there are two ozone molecules from one photon absorbed by O2. Source: Wikimedia Commons. Author: Rainald62.

In a bit of good fortune for oxygen lovers like us (as we discussed last time), plants also acquired a second bacterium as a new organelle (i.e., chloroplasts). From this, plants evolved into net absorbers of CO2, and net producers of oxygen.

Cooperation and competition

This dynamic is brimming with cooperation and competition. In an incidental way, animals that absorb oxygen and produce CO2 as waste are cooperating with plants that absorb CO2 and produce oxygen as waste.

In a more deliberate sense, we cooperate by spreading the genes of the plants and animals that we cultivate, many of which only exist in large numbers around the world because of human selection. In this way, cultivating and eating plants and animals includes aspects of cooperation.

Other animals have a similar, but less intentional, cooperative dynamic with plants, spreading plants’ genes by acting as pollinators or by excreting their seeds. Some animals even bury plant seeds, like the forgetful (but accidentally helpful) squirrel.

Squirrels sometimes act as accidental gardeners by burying and forgetting about nuts, such as acorns, also known as oaknuts (aka ‘acorns’). In this way, many oak trees have been planted by forgetful squirrels. Source: Wikimedia Commons. Author: Paul Johnston.

It’s not all sunshine and rainbows, however, as competition over food is also one of the oldest sources of tension in the living world. Most organisms are always at risk of becoming someone else’s prey, and competition over resources remains central to everyday life for most organisms.

Even plants are far from helpless spectators, with a list of frightening poisons lying in wait for hungry and unwary animals. For example, alongside cliches like poison berries, apple seeds contain very small amounts of compounds that can combine to produce cyanide when the seeds are crushed. This is often suggested to be a defence mechanism against overeating and wanton destruction of seeds by large and greedy animals.

There are also many competitive sides to our cultivation of certain plants and animals. Most obviously, people compete for resources as both individuals and groups. Our cultivation of plants and animals usually occurs at the expense of other organisms as well, and we’re known to destroy entire ecosystems to support vast stretches of farmland.

Further, the plants and animals we use for food only temporarily benefit from our cooperation, as their side of the ‘bargain’ is that their nutrients and genetic material are destined for our stomachs or the bin. As usual, the yin and yang of cooperation and competition are closely intertwined and sewn deep into the fabric of biology and evolution.

Next time

This is all very neat, but something doesn’t quite add up. We’re told that there’s a deal at the heart of eukaryotic life: mitochondria provide a healthy supply of ATP in exchange for a safe and resource-rich environment inside their host organism. Sure enough, that’s how it works today.

But under regular circumstances, a bacterium, like other organisms, has no interest in sharing its precious ATP. The ancestor of our mitochondria was a free-living bacterium that was engulfed by an archaeon. In consequence, it almost certainly wouldn’t have even been able to share ATP with the archaeon when their union began.

Evolution clearly found ways to deal with this problem, and nowadays sharing ATP is one of a mitochondrion’s defining features. But this could only have emerged gradually some time after the ancestral bacterium and archaeon began their endosymbiosis. So, how did the band stay together in the meantime? We’ll get to that next time when we discuss free radicals and the dark side of oxygen. Until then!