Mitochondria Are Alive

Mitochondria are why I’m a Rare Earther.

In Earth’s history, mitochondrial endosymbiosis occurred once. Without that you don’t have the energy budget for complex life. Moreover, there may be a narrow window where it can happen: modern microbiology has defences and selection pressures that it make inhospitable to the hobbling chimeræ the first mitochondrial cells would have been.

Until mitochondria, the emergence of life from nothing is plausible. With mitochondria, its progression to complex, multicellular and intelligent life makes sense. Both processes in small steps can be replicated, more or less, in the lab. But that one moment is not and has not been. As a result, I think the universe has lots of living slop but very few plants and animals.

(Aside, look at ATP go: https://www.youtube.com/watch?v=lUrEewYLIQg&t=939s)

This article is framed as if there is something novel and profound here, but the "aliveness" of mitochondria is simply a matter of how we choose to apply the label "life" - a human linguistic construct that exists independently of the biological phenomena. This is not a new discussion - science has been considering this question for many decades, just as it has with viruses. These all come down to arguments about semantics and don't add anything to the science.

Mitochondria are fascinating and there is still a huge amount to learn about them but they are totally dependent on the cell's machinery. Most of their genes, the code for their structure, are in the nuclear DNA. A glaring omission if you are trying to make the case that mitochondria are independently living. My heart can exist independently of me, and be transplanted into other people, but does it mean that it is alive?

The implication of the whole article is that there something we have missed. This really isn't the case. Lynn Margulis's endosymbiotic origin of mitochondria was challenged by many, and it did spark a scientific debate - that's how science works. She won the argument comprehensively decades ago and is well established science. There have been many such endosymbiotic events in the history of life - there are subfields of evolutionary biology that study these processes.

This article managed to hit two classic science journalism cliches in just the first few paragraphs.

(1) “Someone hypothesizing a very dramatic theory with weak evidence was considered wrong by most colleagues but later vindicated when strong evidence emerged”. (No mention of thousands of other dramatic hypotheses that turned out wrong.)

(2) “You may have heard in unsophisticated popularization that [philosophical claim ultimately hinging on semantic distinction] was false, but really it’s true [assuming my preferred semantics]”.

Aren't we all tired of this yet? Aren’t science journalists embarrassed by this stuff?

Any time I read a mitochondria post like this, I strongly recommend that others who find the topic interesting check out Power, Sex, and Suicide by Nick Lane.

Excellent book!

>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.

This assertion is made but not supported. I don't think I understand the importance of this distinction, assuming that everyone already agrees about the evolutionary and mechanical facts about mitochondria, but as far as I can tell, no one disagrees that mitochondria were originally free living cells, or that they have their own DNA, or any of the other relevant facts about their origins or how they work in the cell. It's merely an argument about what it means to be alive. Which is philosophically interesting, but practically unimportant for the practice of biology.

This seems like a purely semantic debate with no broader importance.

I read the article waiting for an answer to the question "in what operational sense does this matter?" but it never arrived.

The question posed is whether we consider mitochondria to be "alive". It's just a word, who cares. What do we do differently given this assumption?

Random thought after reading all the philosophical and semantics tangents in the comments here:

A good example of a memetic equivalent of endosymbiosis could be Christianity - Catholicism in particular. Historically, as Christianity spread around the world over the two millenia, it would often adapt and absorb indigenous beliefs and practices of converted populations[0]. Many would die out over time, but some got integrated into the core and exported globally.

It's just the right time of year to think about Christmas[1]. Can you imagine Christianity without one of its two core holidays? That makes it probably the closest memetic equivalent of a mitochondria - you can still see in it the distinct outline of an ancient Roman festival that was absorbed early on, but all of its memes live on in Christianity. In our times, the holiday is vital to the overall faith, and itself could not exist independently[2].

--

[0] - I've always been taught that this was intentional slack to make it easier for people to accept a new religion, but nowadays I feel it might have been a fundamentally unavoidable outcome. Maintaining organizational coherence and belief consistency at a scale of a whole continent requires communication and bureaucratic technologies that didn't exist until the last 100-200 years.

[1] - Or at least so most shops would have me believe; in western commercial calendar, Christmas starts when Halloween ends.

[2] - Well okay, I admit this might be a weak part of the analogy - in the western world, Christmas got commercialized to the point it could likely survive as an independent secular tradition.

The fact that every child on the planet is religiously taught that the mitochondria is the powerhouse of the cell is all the evidence I need that we're upholding a primordial contractual agreement and these are the conditions to which we are beholden.

Name a single biological entity that has a better PR department. The only one that comes close is Athlete's Foot, which makes the victim sound cool.

Key fact (left out of the article): most of the mitochondria's essential proteins, including those for ATP/energy synthesis, are produced by the host cell from the host cell's DNA. So yes, mitochondria have some DNA and do replicate, but no, their cell is not just an "environment" for them.

Also interesting: mitochondria can join (often to rescue one failing due to transcription errors) and be transported to other cells across bridges (to supercharge the recipient, as they want to do now for immune cell therapy).

It's such highly unlikely chance events that make me think we really are alone in the universe (we = a sentient civilizational lifeform). There's just no way the long series of extremely improbable events that led to our rise was replicated anywhere else, and it took the sheer vastness of this universe for it to have emerged even once.

this is the first ive heard of mitochondria replicating separately and distinctly from the host cell, how fascinating!

Are we saying that mitochondria have their own life cycle inside of a cell? living/dying/replicating in the span of the "life" of a single host cell? When a host cell reproduces, how does the mitochondria get produced in the new cell to get things started?

Cant wait to research this later.

I don’t understand the headline (yes I skimmed the article). Why would mitochondria not be alive? What does that even mean?

Here is an animation of the Mitochondria in action. The mitochondria has two cell membranes. The gap in between is called the intermembrane space. It is also positively charged with protons. There are complexes 1-4 which continuously pump protons into this space. The ATP synthase molecule harnesses these protons, similar to a water wheel harnessing the flow of water, to make ATP which is the energy molecule the cell uses.

https://youtu.be/LQmTKxI4Wn4?si=i7TpeoV3o_mCWpZF

a lot of focus on the definition of "alive" in the comments, but i think that the weight of this rests on it being a step toward confirming the endosymbiotic relationship theory which states that mitochondria were potentially part of another eukaryotic cells carrying what would become mitogchodria were engulfed by another cell. this affected cellular development by outsourcing energy production for the cell itself. a lot of times the results seem "self-evident" but you still have to find evidence to support or reject a theory and this seems like a step in that direction.

They are obviously alive, but also we are obviously a colony organism. The various bacteria we transmit from mother to child, the mitochondria inherent to our cells, all of this stuff is just part of a self-similarity of life from top to bottom. With sufficient zoom-out, we need not treat individuals (or pairs) as the only unit of life replication.

This feels a lot like the debate about whether Pluto is a planet: what we're really trying to figure out here is whether we can figure out a definition for a concept that includes all the things we think should be included, and excludes all the things we think should be excluded -- and the meta conversation is: can we all agree on what should be included/excluded? That's a bit of a dance, since a cleaner and simpler definition can swing people's opinion about inclusion/exclusion, so the influence goes both ways.

> If we think of mitochondria as non-living organelles, how will we ever harness their full potential?

"Alive" is a fuzzy boundary in concept space that helps humans navigate a fractally complex world. It's not a fact about mitochondria that either hides or reveals structure. We can harness the potential of viruses, and reasonable people can disagree on whether they are alive.

> Mitochondrial DNA mutates 100-1,000 times faster than the human genome

This statement is very interesting for two reasons:

1) We not consider mitochondrial DNA as part of the human genome when it's clearly is and can be used to establish the maternal genetic lineage.

2) Traditionally, we always think of telomere reduction and genetic mutations as the root cause of aging but not mitochondrial genetic damages.

> If one considers bacteria as living entities — and all biologists seem to — then it is impossible to explain why mitochondria are not.

There seems to be a strange, half-hubris, half-pride vein that runs through Humanity that would see us as lesser for being hosts to benevolent bacteria, despite us very obviously being unable to survive without benevolent bacteria.

Okay, what about the Earth? If mitochondria are alive, you must also consider the Earth as being alive too. Personally, I think it's a simple answer. Here's my positively b reasoning on the topic for anyone daring enough. It can be a very blurred line, but much of that is our shadow. Mitichondria are more alive than they are dead. Simply because they exist as potential and can go on and are intended for this, for lack of better words. Where as a rock will not come alive, no matter the conditions. We hope.

Maybe we should think of it like we do for other forms of energy and how I be thought we did think of it already but was of biochemical energy expressions. Along with kinetic energy, potential energy, chemical energy. Surely there is a number determined for the maximum lifetime energy output potential (work) of a single mitochondrion. While it is plain and simple, that's just life for you

Okay, what about the Earth? If mitochondria are alive, you must also consider the Earth as being alive too. Personally, I think it's a simple answer. Here's my reasoning on the topic for anyone daring enough. It can be a very blurred line, but much of that is our shadow. Mitichondria are more alive than they are dead. Simply because they exist as potential and can go on and are intended for this, for lack of better words. Where as a rock will not come alive, no matter the conditions. We hope.

Maybe we should think of it like we do for other forms of energy and how I be thought we did think of it already as biochemical energy expressions. Along with kinetic energy, potential energy, chemical energy. Surely there is a number determined for the maximum lifetime energy output potential (work) of a single mitochondrion. While it is plain and simple, that's just life for you.

Wonerful! This article is a mind-meld of Humberto Maturana’s work on autopoiesis with almost any of Nick Lane’s deep discussions of bioenergetics e.g., the wonderful book “ Power, Sex and Suicide: Mitochonria and the Meaning of Life” or his equally strong book “Transformer: The Deep Chemistry of Life and Death” that is focused on the Kreb’s cycle. He brings biochemistry and bioenergetics alive in a way that will impact your thinking.

Maturana and Valera gave a brilliant definition of “living” in Autopoiesis and Cognition: The Realization of the Living” (1980). But their writing style will make this a tough read. Terry Winograd write a useful summary if Maturana’s philosophy in his computer science classic “Computers and Cognition”.

> My heart can exist independently of me, and be transplanted into other people, but does it mean that it is alive?

Interesting analogy, made more interesting still if one replaces "heart" with "brain."

And what if you reverse mitochondria and host cell? If you remove the mitochondria, is the host cell still alive? The analogy would be to remove the heart from its 'host' environment, and asking if the remaining body still can be called alive.

"for a man cut open is, so far, not a man. And if you do not sew him up speedily you will not see organs, but death."

I'll add the following to the conversation :

https://x.com/niko_kukushkin/status/1854593093636350387 and https://web.archive.org/web/20170506064530/https://inference...

As a layman I'm kind of baffled by the enduring pop-sci interest in mitochondria.

To me the far more interesting organelle is the ribosome. This elegant self-replicating machine that is highly conserved across lifeforms is fascinating and much closer to the origin of life than mitochondria.

How did ribosomes evolve? Are the ribosomes that we see in modern organisms the first design that did evolve? Why are they highly conserved?

Are ribosomes alive as well?

Today I learned that mitochondria are the only organelles that replicate “on their own” inside a cell, while the other organelles just bud off the preexisting ones. I wonder how they are signaled to do so though.

Reminds me of sea slugs that eat plants and then integrate their chloroplasts to produce energy, or my dad who kept swapping the same Honda motor through all our go karts because it was too good to get rid of.

I'd been taught mitochondria maybe came from bacteria back in high school 40 years ago but I didn't realise till now that Lynn Margulis also proposed the cell nucleus arose in a similar way.

(paper https://pmc.ncbi.nlm.nih.gov/articles/PMC34369/)

If you want a fun scifi horror novel to read related to this topic, check out Parasite Eve by Hideaki Sena. It's the novel that inspired the PSX game. The whole plot revolves around mitochondria and was inspired by the author's time as a grad student. I read it a few months ago and really enjoyed it.

Consider that there are thousands of mitochondria (MT) in an individual muscle cell. Cell diagrams often make it look like there is one MT organelle. It's highly misleading.

Single cell bacteria have thousands of genes. MT have a few dozen genes. Many of the genes that regulate MT are contained in the cell's nucleus.

“In the early 20th century, Albert Einstein and Claude Shannon laid out the three pillars of the physical world: matter, information, and energy.”

I’ve yet to see a convincing argument that information has independent existence. The notion is ontologically absurd on its face.

I agree completely with all the points made in the article and would double down on the critique of the philosophy of biology as a discipline and science itself: namely that is has historically evolved as a mere system of typologies and that this is so settled in and so sacrosanct that biology is such a superstition with human-made categories a couple hundred years ago and not a real science.

We see the exact same things also when discussing what is a species and also completely disregarding the reality of horizontal gene transfers etc in the strict, traditional trees.

The models are quite wrong and even reduced wrong.

There is this one famous article that shows how traditional biology would go and analyze a transistor radio, namely just label its assumed components!

Here is the discussion: https://news.ycombinator.com/item?id=31697757

I thought the Mitochondria Liberation Front was defunct. Are people getting back into this type of linguistic debate? Anyway, uplifting as a whole is pretty sketchy and I'm not sure there's too much point.

Feels analogous to the CPU and the Management Engine heh.

I once asked a biologist “using today’s understanding, what is life?” She answered with ”the more we learn, the more I ask myself what is biology?”

For a fictional macro version of the Margulis hypothesis, I'd recommend 'Alien Clay' by Adrian Tchaikovsky

Interesting argument

> control bioenergetics across the eukaryotic tree of life.

What types of outcomes do we unlock when we can control bioenergetics?

"In the early 19th century, "

With that level of proofreading, I'm not sure what else was wrong in the article...

It reminds me the game Parasite Eve.

Surely I can't be the only one who read this as midichlorians and thought it was something to do with star wars. Actually feel a little ashamed about that.

the mitochondria are alive, and they're doing just fine

Pointless word games.

Is this a blog post or... Why does this have 305 comments?

Talking about what is considered "alive" is an interesting exercise, and shows just how fuzzy those boundaries can be sometimes. But I really don't see how this has any practical impact on how we study mitochondria.

> If we think of mitochondria as non-living organelles, how will we ever harness their full potential?

Whenever anyone uses the "harnessing [its] full potential" cliché, my bullshit alarm starts buzzing. I don't think this article is bullshit, but...we can "harness" as much "potential" as mitochondria have whether we consider them alive or not.

So what now? We give them rights?

I expect such lively news to make this comment section the powerhouse of the front page. :^)

I'm sure there's a fantastic midi-chlorian joke here.

If we label mitochondria as alive, that would mean prison laborers must count as living, too.

I wonder what mitochondria dream about. Do they have elections? Politics? Their own understanding of the universe, that somehow ends on the skin surface?

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