Mitochondria Are Alive - Asimov Press

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Mitochondria Are Alive<br>The physical world is an intricate dance between matter, information, and energy. Recognizing that mitochondria are alive will open new horizons into how we learn about, and build with, biology.<br>Nov 08, 2024

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Audio playback is not supported on your browser. Please upgrade.An opinion essay by Liyam Chitayat<br>The cells within our body are the remnants of an ancient alliance.<br>In a 1967 paper called “On the Origin of Mitosing Cells,” American evolutionary biologist Lynn Margulis proposed an idea that, upon first hearing, seems ludicrous. Her paper, in fact, was rejected by 12 different journals before it was published.<br>Margulis argued that one-and-a-half billion years ago, a primitive eukaryotic cell engulfed an oxygen-utilizing bacterium. But rather than digesting this bacterium — or conversely, the bacterium destroying its newfound host — the two cells gradually entered into an endosymbiotic relationship; the host provided nutrients and protection to the bacterium, and the bacterium supplied energy to the host. Margulis argued that this endosymbiosis event was a seminal “innovation engine” for biological systems, ultimately leading to the modern mitochondrion and chloroplast.<br>Margulis’ theory was attacked and ridiculed, igniting academic hostilities that lasted for decades. Over time, though, biologists began to accept her ideas because the membrane structure and molecular machinery within mitochondria closely resemble that of extant bacteria. Most biologists today, however, also believe that mitochondria have “devolved” into little more than membrane-bound organelles, similar to inanimate components like the endoplasmic reticulum or Golgi apparatus.<br>But a swelling tide of scientific evidence about mitochondrial functions and dynamics suggests otherwise — mitochondria are not just organelles, but their own life forms.

An image from L. Margulis’ 1967 paper, depicting the origins of modern mitochondria.<br>This distinction between “life” on the one hand and “mere membranous structure” on the other may seem trivial, but it’s a symptom of a deeper problem. Defining mitochondria as “nonliving” isn’t just a classification mistake, nor a question of word choice. Rather, it is a fundamental misunderstanding of the nature and role of mitochondria. It inherently undermines our understanding of biological systems and deeply influences the tools we build to study them.<br>If we think of mitochondria as non-living organelles, how will we ever harness their full potential?<br>Subscribe to Asimov Press.

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The precise definition of “life” has been debated since the inception of biology as a scientific field. Even today, researchers offer overlapping, but distinct, criteria. Molecular biologists tend to focus on characteristics like metabolism, growth and development, response to stimuli, reproduction, and the ability to process information or evolve. This definition uses “checklists” to determine whether or not an organism is alive.<br>Biophysicists often take a more rigorous approach, defining life by means of energetic terms. Physicists Erwin Schrödinger and Ilya Prigogine said that living organisms maintain order despite the universe's tendency towards increasing entropy, a measure of how dispersed or disordered the energy within a system is. Living systems maintain far-from-equilibrium states, constantly exchanging matter and energy with their environment to sustain highly organized structures. Cells take in low-entropy inputs, such as food or sunlight, and expel high-entropy outputs, including waste.<br>Regardless of which definition one chooses, mitochondria are clearly alive.<br>Mitochondria carry their own genomes and express their own genes within their lumens, an internal pocket of watery space, using biomolecules distinct from the cell’s nucleus. Mitochondria also replicate and divide through binary fission, much like bacteria. If one considers bacteria as living entities — and all biologists seem to — then it is impossible to explain why mitochondria are not.<br>From a thermodynamic perspective, mitochondria take in low-entropy inputs from their host cell, such as glucose or fatty acids, and expel high-entropy outputs, including carbon dioxide and water. Mitochondria also pump out protons through their inner membrane to maintain an out-of-equilibrium thermodynamic balance, using the resulting gradient to produce the ATP molecules that fuel cellular functions, from DNA replication to protein synthesis.<br>From the molecular biologist’s perspective, a mitochondrion’s role is not limited to simple energy generation, either. Mitochondria also process information and interact with their environment, much like a human cell. They monitor steroid hormones, oxidative stress, heat, ATP levels, secondary metabolites, and many more molecules floating through their environment, the cell’s...