Science Quiz

It comes from a magazine headline, and the headline was right.

In July 1957 Scientific American ran an article by the cell biologist Philip Siekevitz under the title "Powerhouse of the Cell". Its standfirst reads: "It is the mitochondrion, a small body which appears to play a central role in the oxidation of foodstuff. Its structure, as revealed by the electron microscope, mirrors its function." Seven decades later that title is the best-known sentence in cell biology, quoted by people who could not name one other organelle.

It survived because it is true. Mitochondria really are where most of a cell's usable energy is made, in the form of a molecule called ATP.

The stranger half never made it into the phrase. The powerhouse is a captured bacterium. It kept its own genome, you inherited it from your mother alone, and some of your cells carry two thousand of them.

Key Takeaways

• The phrase is the title of Philip Siekevitz's article in Scientific American Vol. 197 No. 1, July 1957, page 131.
• The US National Human Genome Research Institute defines mitochondria as organelles that "generate most of the chemical energy needed to power the cell's biochemical reactions", stored in a molecule called ATP.
• Mitochondria let a cell extract 15 times more ATP from sugar than it could by glycolysis alone, according to Molecular Biology of the Cell.
• The NHGRI calls human mitochondrial DNA a circular chromosome. MedlinePlus gives its size as about 16,500 base pairs and its contents as 37 genes, 13 of them encoding enzymes of oxidative phosphorylation.
• The "powerhouse" image of a fixed lump of machinery is the misleading part. Molecular Biology of the Cell describes mitochondria as "remarkably mobile and plastic organelles", constantly changing shape, fusing and separating again.

Who first called mitochondria the powerhouse of the cell?

Philip Siekevitz, or at least the editor who set his headline, in the July 1957 issue of Scientific American. The article is catalogued as Vol. 197 No. 1, page 131, with the digital object identifier 10.1038/scientificamerican0757-131.

The idea that mitochondria are where a cell burns its fuel was not new in 1957, and Siekevitz's own summary makes that plain: the mitochondrion "appears to play a central role in the oxidation of foodstuff". The phrasing was what was new. A powerhouse is a building full of generators that exists so everything else can have electricity. That image does an enormous amount of work in four words. It says the organelle is specialised. It says the organelle serves the rest of the cell rather than itself. And it puts the source of the energy in one place.

The timing helped. Understanding what mitochondria do had waited on being able to get intact ones out of a cell at all, and Molecular Biology of the Cell dates that to "procedures developed in 1948 for isolating intact mitochondria". Siekevitz was writing in the first decade when the answer was actually arriving, into a magazine read by people who were not cell biologists. The phrase went into schoolrooms and never left.

What do mitochondria actually do?

They finish the job that starts when you eat something, and they do it far better than the alternative.

The National Human Genome Research Institute puts the definition plainly: mitochondria are "membrane-bound cell organelles" that "generate most of the chemical energy needed to power the cell's biochemical reactions", and "chemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate (ATP)".

The size of the advantage is the part that gets skipped. Breaking glucose down to pyruvate without oxygen releases, in the textbook's words, "only a very small fraction of the total free energy potentially available from the glucose".

Send that pyruvate into a mitochondrion instead. Oxidise it fully to carbon dioxide and water, and the same sugar yields "15 times more ATP" than glycolysis alone. Without mitochondria, the book says, "present-day animal cells would be dependent on anaerobic glycolysis for all of their ATP". That is a quiet way of saying large, active animals would not exist.

The organelle is not spread evenly through a body. The NHGRI's own narration notes that "the muscle has a lot of mitochondria, the liver does too, the kidney as well, and to a certain extent, the brain, which lives off of the energy those mitochondria produce". One liver cell holds 1,000 to 2,000 of them, taking up about one fifth of the cell's volume.

They are placed rather than scattered. In a heart muscle cell they sit packed between the contracting filaments. In a sperm they are wound tightly around the tail. Both times they are pressed against the machinery that spends the ATP.

How that energy actually gets captured was not settled until 1978, and the answer was stranger than anyone had proposed. The hypotheses of the 1950s all assumed a direct chemical handoff between the enzymes that oxidise and the enzymes that phosphorylate.

In 1961 Peter Mitchell said there was no handoff at all. Electron flow pumps protons across the inner membrane instead. That builds what the Nobel Prize press release calls "an electrochemical proton gradient", part concentration difference and part voltage, which Mitchell named the protonmotive force. ATP is made by letting the protons fall back down it.

The Royal Swedish Academy of Sciences is candid about the reception: "This theory was first received with scepticism; but, over the past 15 years, work in both Mitchell's and many other laboratories have shown that the basic postulates of his theory are correct." He was awarded the 1978 Nobel Prize in Chemistry for it, alone. The press release records that Mitchell had taken to calling his principle "proticity", by analogy with electricity. It also observes that mitochondria and chloroplasts are "remarkably like miniaturized solar- and fuel-cell systems". The 1957 headline was closer to literal than its writer could have known.

Why do mitochondria have their own DNA?

Because they used to be somebody else.

Every other organelle in your cells runs on instructions from the nucleus. Mitochondria do not, entirely. The NHGRI glossary states it flatly: "Mitochondria contain their own small chromosomes." MedlinePlus gives the specification. Human mitochondrial DNA "spans about 16,500 DNA building blocks (base pairs)" and "contains 37 genes, all of which are essential for normal mitochondrial function". Thirteen of the 37 encode enzymes of oxidative phosphorylation. The rest make the transfer RNA and ribosomal RNA needed to build those thirteen proteins on site.

It reads like a bacterial genome because it descends from one. Most mitochondrial DNA is circular, "like a typical bacterial genome", and it is packaged without the histone proteins that wrap DNA in the nucleus. Bacteria do not use histones either. The organelle even looks the part, drawn in textbooks as a stubby cylinder half a micrometre to a micrometre across, at bacterial scale.

The mitochondrial genome	Figure	Source
Length in humans	about 16,500 base pairs	MedlinePlus
Share of total nuclear genome size	less than 0.001%	Molecular Biology of the Cell
Genes carried	37	MedlinePlus
Of those, encoding oxidative phosphorylation enzymes	13	MedlinePlus
Smallest known, in the malaria parasite Plasmodium falciparum	under 6,000 base pairs	Molecular Biology of the Cell
Largest known, in some land plants	over 300,000 base pairs	Molecular Biology of the Cell

The explanation is the endosymbiont hypothesis. An ancestral cell swallowed a bacterium and did not digest it. On the textbook account, mitochondria and chloroplasts descend from bacteria taken inside another cell more than a billion years ago, by a host that then, in its words, "subverted" the newcomer's oxidative phosphorylation "for their own use".

The idea is older than most people assume. Michael Gray's fiftieth-anniversary assessment in Molecular Biology of the Cell records that endosymbiotic origins "first emerged in various forms in the late 19th and early 20th centuries before fading from mainstream biological view".

What brought them back was a 1967 paper in the Journal of Theoretical Biology titled "On the origin of mitosing cells", by "Lynn Margulis (then Lynn Sagan)". Its abstract, as indexed by the US National Library of Medicine, proposes that "three fundamental organelles: the mitochondria, the photosynthetic plastids and the (9+2) basal bodies of flagella were themselves once free-living (prokaryotic) cells".

Gray adds a detail worth keeping. The paper "did not have an auspicious beginning, reportedly having been rejected by more than a dozen journals before eventually finding a home".

He is careful about what held up. The mitochondrial and plastid halves are settled, traced by their genomes to the bacterial groups α-Proteobacteria and Cyanobacteria. The third claim did not survive: that the eukaryotic flagellum came from a swallowed spirochaete. Gray's reason is blunt. "No genome has been associated with the eukaryotic flagellar apparatus despite efforts to find one." A landmark paper can be two thirds right and still be a landmark.

One consequence of that ancestry shows up on family trees. The NHGRI's sentence is: "Generally, mitochondria, and therefore mitochondrial DNA, are inherited only from the mother." The organelle's genome tracks one unbroken maternal line, and that is what makes mitochondrial haplogroups useful for ancestry.

Is the powerhouse of the cell a fair description?

It is accurate and it is thin, which is a different complaint from being wrong.

Nothing in the phrase is false. The problem is that it describes a job rather than a thing, and it invites you to picture a fixed lump of industrial equipment bolted into a corner of the cell. Mitochondria are not that. Time-lapse film of living cells shows them "remarkably mobile and plastic organelles, constantly changing their shape and even fusing with one another and then separating again", travelling along microtubules and forming long moving chains. There are hundreds to thousands per cell, and the population is continuously merging and splitting.

The genome is not tidy either. Gray quotes the observation that "the mitochondrial genetic system exhibits unmistakable signs of great inter- and intra-species diversity", and summarises fifty years of comparative work in three words: "in mitochondria, anything goes."

And the machinery Mitchell described turned out not to be reserved for making ATP at all. The Nobel citation lists other processes now understood to run on the same protonmotive principle, including "the uptake of nutrients by bacterial cells, cellular and intracellular transport of ions and metabolites, biological heat production, bacterial motion". A proton gradient across a membrane is a general-purpose way of storing and spending energy, and ATP synthesis is one customer among several.

What happens when the machinery fails is where the NHGRI narration turns unusually frank, because a defect in the mitochondrial pathways produces "symptoms in the muscle, in the brain, sometimes in the kidneys as well; many different types of symptoms. And we probably don't know all of the different diseases that mitochondrial dysfunction causes." The chapter is still open.

So keep the phrase. It got a generation of people to remember one true thing about the inside of a cell, which is not nothing. A memorable label is a real achievement, and it is also the thing a five-question IQ test cannot measure: how much sits behind the answer you picked.

Just treat it as a job title. Job titles are usually the least interesting fact about anyone. This one belongs to a former bacterium that moved in, kept its own paperwork, and has been running the electricity ever since.

That was one question of five. The other four went at gold's symbol, the bone count, what holds the planets in orbit and what plants take out of the air, and the other short quizzes work through the rest.

Frequently asked questions

Why is the mitochondria called the powerhouse of the cell?

Because it is where most of a cell's usable energy is produced, and because a Scientific American article carried that exact title in July 1957. The National Human Genome Research Institute defines mitochondria as organelles that "generate most of the chemical energy needed to power the cell's biochemical reactions", stored as ATP. The scale of the advantage justifies the name. Fully oxidising sugar inside a mitochondrion yields 15 times more ATP than breaking it down without oxygen, and animals with high energy demands depend on that margin. Strictly, "mitochondria" is the plural and "mitochondrion" the singular, so the grammatical version of the phrase is "mitochondria are the powerhouses of the cell".

Who discovered mitochondria?

No one person, and that is why no name is attached. Molecular Biology of the Cell notes only that mitochondria "are large enough to be seen in the light microscope, and they were first identified during the nineteenth century". Understanding what they were for came much later and depended on being able to isolate intact ones, which the same source dates to techniques developed in 1948. The mechanism by which they capture energy was not settled until Peter Mitchell's chemiosmotic theory, proposed in 1961 and recognised with the 1978 Nobel Prize in Chemistry.

Do mitochondria really have their own DNA?

Yes, and it is the only DNA in a human cell that does not sit in the nucleus. MedlinePlus gives its size and contents: about 16,500 base pairs carrying 37 genes, thirteen of which encode enzymes for oxidative phosphorylation while the remainder produce transfer RNA and ribosomal RNA. Its shape comes from the NHGRI, which calls mitochondrial DNA "the circular chromosome found inside the cellular organelles called mitochondria". A circular chromosome packaged without histones is what a bacterial genome looks like. That resemblance is the strongest piece of evidence that mitochondria descend from free-living bacteria.

Are mitochondria inherited only from your mother?

Generally, yes, and the hedge is the NHGRI's own. Its glossary entry reads in full: "Generally, mitochondria, and therefore mitochondrial DNA, are inherited only from the mother." It does not say what the exceptions are, so neither will this. The practical effect is that your mitochondrial genome traces one unbroken maternal line back through your mother, her mother and so on, untouched by any male ancestor. That is the basis of mitochondrial haplogroup testing, and it is also why mitochondrial disorders do not follow the inheritance patterns people expect from nuclear genetics.

Was Lynn Margulis right about endosymbiosis?

About mitochondria and chloroplasts, yes, and on the evidence since, decisively. Her 1967 paper appeared under the name Lynn Sagan and was, by Michael Gray's account, rejected by more than a dozen journals first. Genome comparisons have since traced mitochondria to the bacterial group α-Proteobacteria and plastids to Cyanobacteria. The third part of her argument, that the eukaryotic flagellum also came from a swallowed bacterium, has not held up, because no genome has ever been found associated with the flagellar apparatus. Gray's assessment is that not all of her ideas were accepted "for want of compelling evidence", while her promotion of symbiosis "unquestionably had a major influence" on everything that followed.

Sources

• Philip Siekevitz, "Powerhouse of the Cell", Scientific American Vol. 197 No. 1, July 1957, page 131: scientificamerican.com/article/powerhouse-of-the-cell. Source of the title, the author, the publication details and the quoted standfirst about the oxidation of foodstuff.
• National Human Genome Research Institute, Talking Glossary of Genomic and Genetic Terms, "Mitochondria": genome.gov/genetics-glossary/Mitochondria. Source of the definition, the ATP sentence, the maternal-inheritance line, "Mitochondria contain their own small chromosomes", and the narration quoted on tissue distribution and on mitochondrial disease.
• National Human Genome Research Institute, Talking Glossary, "Mitochondrial DNA", narration by Lisa H. Chadwick, Deputy Director, Division of Genome Sciences: genome.gov/genetics-glossary/Mitochondrial-DNA. Source of the haplogroup point and of the quoted description of mitochondrial DNA as "the circular chromosome found inside the cellular organelles called mitochondria".
• Bruce Alberts and others, Molecular Biology of the Cell, 4th edition, Garland Science 2002, "The Mitochondrion": ncbi.nlm.nih.gov/books/NBK26894. Source of the fifteenfold ATP figure, the quoted line about the small fraction of free energy released by glycolysis, the 1948 isolation date, the count of mitochondria per liver cell and their share of cell volume, the cylinder dimensions, the plasticity and fusion description, the placement in heart muscle and sperm, and the FAQ's quotation that mitochondria "are large enough to be seen in the light microscope, and they were first identified during the nineteenth century".
• Bruce Alberts and others, Molecular Biology of the Cell, 4th edition, "The Genetic Systems of Mitochondria and Plastids": ncbi.nlm.nih.gov/books/NBK26924. Source of the circular-genome and no-histones comparison with bacteria, the genome size range from Plasmodium falciparum to land plants, the share of the nuclear genome, and the quoted statement of the endosymbiont hypothesis.
• MedlinePlus Genetics, US National Library of Medicine, "Mitochondrial DNA": medlineplus.gov/genetics/chromosome/mitochondrial-dna. Source of the base-pair count, the gene count, the split between oxidative-phosphorylation enzymes and RNA genes, and the hundreds-to-thousands figure per cell.
• The Nobel Prize in Chemistry 1978, press release of 17 October 1978, Royal Swedish Academy of Sciences: nobelprize.org/prizes/chemistry/1978/press-release. Source of the award citation, the 1961 date, the protonmotive force and proton-gradient description, the "first received with scepticism" quotation, the "proticity" coinage, the solar-and-fuel-cell comparison, and the list of other processes running on the same principle.
• Lynn Sagan, "On the origin of mitosing cells", Journal of Theoretical Biology Vol. 14 No. 3, March 1967, pages 255 to 274, as indexed by the US National Library of Medicine: pubmed.ncbi.nlm.nih.gov/11541392. Source of the quoted proposal about the three fundamental organelles, taken from the abstract in the MEDLINE record.
• Michael W. Gray, "Lynn Margulis and the endosymbiont hypothesis: 50 years later", Molecular Biology of the Cell Vol. 28, 2017, pages 1285 to 1287: doi.org/10.1091/mbc.e16-07-0509. Source of the "then Lynn Sagan" attribution, the rejection-by-a-dozen-journals account, the late-nineteenth-century origins of the idea, the α-Proteobacteria and Cyanobacteria assignments, the verdict on the flagellum claim, the quoted remarks on mitochondrial genetic diversity, and the two phrases quoted in the FAQ, "for want of compelling evidence" and "unquestionably had a major influence".