Power, Sex, Suicide

1. What is the book about as a whole?

It's a book on mitochondria. The book goes into the history of the research on the mitochondria and outlines the leading theories on how eukaryotic life came to be and the key role that mitochondria plays in most of it.

2. What is being said in detail, and how?

Mitochondria are responsible for generation of ATP - fungible energy currency. Mitochondria has:

• Matrix - where the chain starts from food source derived from glucose
• Inner membrane - hard for protons to pass through; where the electron-transport chain sits
• Intermembrane space - where protons accumulatewanting to break into the inner membrane
• Outer membrane - outer boundary that gates protons

Glucose breakdown begins from the matrix and - and its electrons are attracted to the oxygen at the end of the chain. The electron chain progresses through several complexes, stripping electrons while processing 'food'. In response, protons are pumped outside the outer membrane. The way in is through the ATP complex - which generates ATP in the process - the energy currency in a cell.

Here are some more important findings:

• Membrane is essential to keep the proton gradient
• Single-cell bacteria is limited in complexity - volume grows faster than surface area, creating a membrane bottleneck on size
• Eukaryotes likely arose from ancestral mitochondria engulfed by archea
• Eukaryotes arose from one-time event - DNA analysis points to single common ancestor
• Fermentation is energy production without oxygen. It is less efficient but faster. Fermentation happens in our muscles when energy demand increases (i.e. exercise)
• Fractal design of the blood system that provides oxygen means that there is a scaling law - it's energy-efficient to be bigger
• The mitochondria have their own DNA. It's a small fraction of the original bacterial DNA - the rest moved to the nucleus
• A set of mitochondrial DNA is essential for the normal operation of mitochondria. Likely cause is that local DNA allows faster response for energy production issues
• Initially, the balance between archeal host and bacteria was fragile
• Because there are two sets of DNA, when the nucleus DNA is damaged, the mitochondria is left with loads of unused energy, creating free radicals. This likely became the signal for sex in unicellular eukaryotes - a way to combine the nucleur DNA to fix the issue
• Sex within multicellular organisms is bad. A cell is part of a larger system and the system dies the cells start to multiply uncontrollably (cancer). Free radicals became a signal for apoptosis
• Two sexes are the norm because minuscule differences in the generated proteins are detrimental to the normal function. The nucleus selects for only one mitochondrial DNA (from the mother)
• Apoptosis is the programmed cell death. It's triggered based on interplay between internal and external signals and - cuts up the cell without a trace (it's a lot more complex than that)
• Apoptosis leads to "survivorship bias" as cells leave no trace.
• More apoptosis, more strain on surviving cells, leading to aging
• High ATP + high FR (free radicals) -> uncoupling of electrons that relaxes the membrane and letting protons, generating heat. Could lead to cell death eventually
• High ATP + low FR -> the best-case scenario
• Low ATP + high FR -> cell is under stress, apoptosis
• Low ATP + low FR -> low-energy state
• Birds live longer than they "should" given the power scaling - that's because of their lower FR. Flight requires a lot of power to start, leading to idle mitochondria
• The key to prolonging life is likely within free radical research, though antioxidants have proven disappointing

3. Is the book true, in whole or part?

The book convinced me that mitochondria are very important. Biology seems very complex and the author made it clear when he might be wrong.

I understood the claim about sex in single-celled eukaryotes but I felt like the author remained too vague on how sex evolved to be what it is today - how it progressed from single-cell to multicellular.

It feels like a lot of the book is based on DNA analysis - such as the single origin of eukaryotes. And yet, the book shows that DNA analysis has limits - there is an inherent survivorship bias and we have only a small recent snapshot. However, I agree that it's the most likely explanation given what we know.

4. What of it?

Proton gradients are fundamental to life on Earth. Seems like power is a limiting constraint - our structure, size, sexual reproduction and life expectancy are tied to power scheme that was found by evolution - namely the mitochondria.

There's nothing to say that proton gradients are fundamental to all possible life - only that they are fundamental to the life we know. Constraints can be challenged if an alternative exists - and that has an implication for extraterrestrial life.

The book makes a pretty strong case that research to prolong life expectancy must target free radicals. This hasn't been proven for the 20 years after the book was released but I will look into how has the field progressed.