Power, Sex, Suicide

1. Mitochondria: The Powerhouses and Puppeteers of Complex Life

Mitochondria are a badly kept secret. Many people have heard of them for one reason or another.

Multifaceted organelles. Mitochondria are tiny organelles inside cells that generate almost all our energy in the form of ATP. On average, there are 300-400 in every cell, totaling ten million billion in the human body. Essentially all complex cells contain mitochondria.

Ancient bacterial origins. Mitochondria look like bacteria, and appearances are not deceptive: they were once free-living bacteria that adapted to life inside larger cells about two billion years ago. They retain a fragment of a genome as a badge of former independence.

Shapers of life's complexity. Their tortuous relations with their host cells have shaped the whole fabric of life, including:

• Energy production
• Sexual reproduction
• Fertility
• Cell suicide (apoptosis)
• Aging
• Death

2. The Evolutionary Chasm Between Bacteria and Eukaryotes

The void between bacterial and eukaryotic cells is greater than any other in biology.

Bacteria's limitations. Bacteria have dominated the world for two billion years, colonizing all thinkable environments. However, they never evolved into the kind of multicellular organism that a layperson might recognize. Their complexity is curtailed by their need to generate energy across the outer cell membrane.

Eukaryotic leap. The eukaryotic cell appeared much later and, in a fraction of the time available to bacteria, gave rise to the great fountain of life we see around us. This includes:

• Elaborate internal membrane systems
• Specialized organelles
• Complex cell cycles
• Sexual reproduction
• Huge genomes
• Phagocytosis
• Predatory behavior
• Multicellularity
• Large size
• Spectacular feats of mechanical engineering (e.g., flight, sight, hearing)

One-time event. The evolution of the eukaryotic cell was likely a one-time event, bridging the gulf between bacteria and complex life through endosymbiosis.

3. The Hydrogen Hypothesis: A Radical Origin Story

A mutual chemical dependency between two very different prokaryotic cells led to a close relationship between the two.

Symbiotic origin. The hydrogen hypothesis proposes that the eukaryotic cell originated from a symbiotic relationship between two prokaryotes:

1. A methanogen (archaeon) host
2. A hydrogen-producing alpha-proteobacterium (ancestor of mitochondria)

Metabolic interdependence. The methanogen used hydrogen produced by the bacterium, while the bacterium benefited from the methanogen's metabolic by-products. This mutual dependency led to their physical merger.

Gene transfer and transformation. Over time, genes transferred from the endosymbiont to the host, enabling the host to:

• Import organic molecules
• Ferment them in the cytoplasm
• Pass fermentation products to the proto-mitochondria for further processing

This gene transfer and metabolic reorganization transformed the symbiotic relationship into the first eukaryotic cell, capable of thriving in diverse environments.

4. Proton Power: The Universal Energy Currency of Life

Not since Darwin has biology come up with an idea as counterintuitive as those of, say, Einstein, Heisenberg or Schrödinger.

Chemiosmotic theory. Peter Mitchell's chemiosmotic theory revolutionized our understanding of cellular energy production. The key points are:

• Energy is stored as a proton gradient across membranes
• This gradient drives ATP synthesis
• The process is universal across all domains of life

Proton-motive force. The proton gradient creates a proton-motive force, which:

• Has the power of a bolt of lightning over a few nanometers
• Drives ATP synthesis through the ATPase (a molecular motor)
• Powers various cellular processes beyond ATP production

Implications for life's origin. This mechanism is so fundamental that it provides insights into the origin of life itself:

• It's found in all forms of life, including the most primitive bacteria
• It may have evolved in alkaline hydrothermal vents
• It could explain why life is chemiosmotic and why it originated on Earth

5. Why Bacteria Remained Simple: The Geometric Constraint

Bacteria are limited in their physical size, genome content, and complexity, they say, because they are forced to respire across their external cell membrane.

Surface area to volume ratio. As bacteria grow larger:

• Their surface area increases more slowly than their volume
• This reduces their energetic efficiency
• Larger bacteria are less competitive than smaller ones

Energetic limitations. The reliance on the outer membrane for energy generation means:

• Bacteria can't grow too large without losing efficiency
• This precludes the evolution of complex, energy-intensive behaviors like phagocytosis
• It limits the genome size and complexity bacteria can support

Evolutionary pressure. These constraints create a strong evolutionary pressure for bacteria to:

• Remain small
• Maintain a streamlined genome
• Quickly lose any genes that aren't immediately beneficial

This explains why bacteria, despite their biochemical diversity, have remained morphologically simple for billions of years.

6. Mitochondria Enable Complexity Through Energy Internalization

Internalization of energy generation within the cell means that an external cell wall is no longer needed, and so can be lost without inducing fragility.

Breaking the size barrier. Mitochondria allow eukaryotic cells to be much larger than bacteria:

• They generate energy inside the cell, not across the outer membrane
• This frees cells from the surface area to volume constraint
• Eukaryotes can be 10,000 to 100,000 times the volume of bacteria

Enabling new lifestyles. The internalization of energy production:

• Allows the loss of the rigid cell wall
• Enables the cell membrane to specialize in other tasks (signaling, movement)
• Makes phagocytosis possible, allowing predatory lifestyles

Scaling up energy production. As eukaryotic cells grow larger:

• They can maintain energy balance by keeping more mitochondria inside
• This allows for the evolution of larger, more complex organisms
• It provides the energy needed for sophisticated behaviors and structures

7. The Power Laws of Biology: Size, Metabolism, and Complexity

Metabolic rate is defined as the consumption of oxygen and nutrients. If the metabolic rate falls, then each cell consumes less food and oxygen.

Kleiber's Law. As animals increase in size:

• Their metabolic rate increases more slowly than their mass
• This relationship follows a power law: metabolic rate scales with mass^0.75
• This means larger animals are more energetically efficient per unit of mass

Implications for evolution. This scaling law has profound effects on:

• Population density
• Range of travel distances
• Number of offspring
• Time to reproductive maturity
• Speed of population turnover
• Rate of evolution

Debated universal constant. While the exact exponent (0.75) is debated, the general principle holds across a wide range of organisms:

• From single cells to blue whales
• Spanning 21 orders of magnitude in mass
• Applying to various biological traits beyond metabolism

This scaling law provides insights into the evolution of size and complexity in living organisms.

8. Warm-Bloodedness: A Mitochondrial Revolution

If the resting metabolic rate scales with an exponent of less than 1 (it doesn't matter what the precise value is) implies that the energetic demand of cells falls with size—larger organisms do not need to spend as great a proportion of their resources on the business of staying alive.

Aerobic capacity hypothesis. The evolution of warm-bloodedness (endothermy) in mammals and birds was likely driven by:

• Selection for greater aerobic capacity (speed and endurance)
• A linked increase in resting metabolic rate

Mitochondrial density. Endothermy is associated with:

• Higher mitochondrial density in muscles and organs
• Greater aerobic performance (up to 10 times that of similarly sized ectotherms)
• Ability to sustain high levels of activity

Evolutionary trade-offs. The benefits of endothermy come at a cost:

• Mammals use about 30 times more energy than equivalent reptiles
• This requires much higher food intake
• It enables new ecological niches and behaviors, but at a high energetic cost

The evolution of endothermy represents a major metabolic shift, enabled by mitochondria, that opened up new evolutionary possibilities for complex life.

9. Apoptosis: Mitochondria as Arbiters of Cellular Life and Death

If, today, we still succumb to the lawlessness of cancer, what hope had the first individuals?

Mitochondrial control. Mitochondria play a central role in apoptosis (programmed cell death):

• They integrate various cellular signals
• They decide whether a cell should live or die
• If death is warranted, they release proteins that activate the cell's death machinery

Evolutionary origins. The machinery of apoptosis has bacterial origins:

• Most apoptotic proteins were brought by the ancestors of mitochondria
• This suggests apoptosis evolved from conflict between early endosymbionts and their hosts

From sex to death. The apoptotic machinery may have originally evolved to promote sex in single-celled eukaryotes:

• Mitochondria could signal host cell damage through free radical production
• This could stimulate cell fusion and genetic recombination
• Over time, this machinery was co-opted for programmed cell death in multicellular organisms

10. The Troubled Birth of Multicellular Individuals

Cancer can persist because it is rare in younger individuals: if the body were to tear itself asunder by internal squabbles before the community of cells had engineered their own reproduction, though the germ-line, then the individual as a whole would fail to pass on its genes, and the selfish genes would be lost from the population.

Cellular cooperation and conflict. The evolution of multicellularity required:

• Cells to subordinate their selfish interests to the whole
• Mechanisms to suppress cellular rebellion (cancer)
• The evolution of programmed cell death (apoptosis)

Apoptosis as cellular police. Programmed cell death serves to:

• Eliminate damaged or potentially harmful cells
• Maintain the integrity of the multicellular individual
• Balance cell division to regulate tissue size and function

From single cells to complex organisms. The transition to multicellularity involved:

• Resolving conflicts between different levels of organization (genes, organelles, cells)
• Evolving new regulatory mechanisms to coordinate cellular behavior
• Harnessing mitochondrial-derived apoptosis for the greater good of the organism

This troubled birth of multicellular individuals set the stage for the evolution of complex life forms, including ourselves.

Last updated: October 18, 2024