Prokaryotic cells do not have mitochondria. Mitochondria are membrane-bound organelles found exclusively in eukaryotic cells, and their absence is one of the defining differences between the two cell types. But the relationship between prokaryotes and mitochondria is far more interesting than a simple “no” suggests, because mitochondria themselves descended from ancient prokaryotes that were engulfed by another cell roughly two billion years ago. That evolutionary history left traces that still matter today, from why some antibiotics cause side effects to why bacteria never evolved into anything as complex as an animal.
Why Prokaryotes Lack Mitochondria
Prokaryotic cells are structurally simpler than eukaryotic cells. The key distinction is that prokaryotes lack a nucleus and other membrane-bound organelles, while eukaryotic cells contain both.1PubMed Central. Some Liked It Hot: A Hypothesis Regarding Establishment of the Proto-Mitochondrial Endosymbiont During Eukaryogenesis Mitochondria fall squarely into the membrane-bound organelle category: they are surrounded by a double membrane, carry their own small genome, and run the oxygen-dependent process that generates most of a cell’s energy supply. None of that machinery exists inside a bacterium or an archaeon.
That does not mean prokaryotes cannot produce energy. They absolutely can, and they use essentially the same core chemistry. The difference is where the chemistry happens. In a eukaryotic cell, the energy-generating reactions are tucked inside mitochondria. In a prokaryote, those reactions take place directly on the cell’s own outer membrane. ATP synthase, the protein complex that actually assembles ATP molecules by harnessing a flow of protons across a membrane, is found in bacteria as a monomer embedded in the plasma membrane, while in mitochondria it forms rows of dimers along the folds of the inner membrane.2eLife. Structure of a bacterial ATP synthase The enzyme is closely related in both settings. Prokaryotes simply run the whole operation at the cell surface instead of delegating it to an internal compartment.
How Mitochondria Came From Prokaryotes
The reason mitochondria resemble bacteria is that they once were bacteria. The endosymbiotic theory, championed by Lynn Margulis in her landmark 1967 paper “On the Origin of Mitosing Cells,” proposed that mitochondria originated when an ancient cell swallowed a bacterium and, instead of digesting it, kept it around as an internal energy factory.3PubMed Central. Lynn Margulis and the endosymbiont hypothesis: 50 years later The idea was initially met with skepticism, but morphological, biochemical, and genomic evidence has since confirmed the broad strokes of her hypothesis.4PubMed. On the origin of mitosing cells: A historical appraisal of Lynn Margulis endosymbiotic theory
Viewed through its genome, the mitochondrion is of unquestioned bacterial ancestry, originating from within the alphaproteobacteria, a large and diverse group of bacteria that includes many free-living species today.5PubMed Central. Mitochondrial evolution Evidence from enzyme studies adds further support: the manganese-containing superoxide dismutase found in mitochondria shows strong similarity to the prokaryotic version, consistent with an endosymbiotic origin.6PubMed. Phylogenetic distribution of superoxide dismutase supports an endosymbiotic origin for chloroplasts and mitochondria Researchers are still narrowing down which lineage of alphaproteobacteria is the closest living relative of the ancestor that became the first mitochondrion. One recent analysis using multiple independent approaches identified the genus Iodidimonas as a strong candidate, though this remains an active area of investigation.7bioRxiv. On the bacterial ancestry of mitochondria: new insights with triangulated approaches
The Host Cell That Swallowed a Bacterium
Knowing that mitochondria came from bacteria raises a natural follow-up: what kind of cell swallowed that bacterium in the first place? The answer, based on a flood of genomic data in recent years, points to archaea, specifically a lineage called Asgard archaea. The last eukaryotic common ancestor already contained a mitochondrion derived from an alphaproteobacterium enclosed within an archaeal host cell.1PubMed Central. Some Liked It Hot: A Hypothesis Regarding Establishment of the Proto-Mitochondrial Endosymbiont During Eukaryogenesis Asgard archaea, discovered over the past decade, carry genes for proteins that were previously thought to be exclusively eukaryotic, including components involved in membrane trafficking and cytoskeletal function.8PubMed. Asgard archaea illuminate the origin of eukaryotic cellular complexity
A 2025 analysis in Nature refined this picture further, concluding that key features of eukaryotic cell organization evolved in the Asgard lineage before the capture of the alphaproteobacterial endosymbiont, with additional genes acquired from other bacteria both before and after endosymbiosis.9PubMed Central. Dominant contribution of Asgard archaea to eukaryogenesis In other words, the merger that created the first proto-eukaryote was not a single event between two partners but an ongoing process of gene mixing across lineages. The mitochondrial acquisition was the pivotal step, but it happened against a background of horizontal gene exchange that reshaped the host cell’s genome over time.
What Mitochondria Made Possible
One of the most profound consequences of acquiring mitochondria was energetic. Prokaryotes generate ATP across their plasma membrane, which means their energy output scales with their surface area. As a cell gets bigger, its volume grows faster than its surface area, and this imposes a hard ceiling on how large and genetically complex a prokaryote can become. Mitochondria broke through that ceiling. By internalizing the energy-generating membranes and the genes needed to control them locally, mitochondria allowed the host cell to expand its total bioenergetic membrane area over several orders of magnitude.10PubMed Central. Energetics and genetics across the prokaryote-eukaryote divide
The downstream effects were enormous. As mitochondrial genomes shrank through gene loss and transfer to the nucleus, the nuclear genome was free to expand, in principle by more than 200,000-fold compared to a typical prokaryote.10PubMed Central. Energetics and genetics across the prokaryote-eukaryote divide The resulting thousands-fold increase in energy availability per gene gave eukaryotes the capacity for more genes, larger genes, far more non-coding DNA, greater regulatory complexity, and vastly more protein production per gene.11Current Biology. How energy flow shapes cell evolution That is the energetic foundation behind everything from multicellularity to brains. Without the mitochondrial partnership, none of it could have happened, and that is ultimately why prokaryotes, despite their extraordinary biochemical versatility, have remained comparatively simple in their morphology for billions of years.
How Mitochondria Still Resemble Bacteria
The bacterial ancestry of mitochondria is not just historical trivia. The structural and molecular similarities between modern mitochondria and bacteria are extensive and have real consequences. Mitochondria retain their own circular DNA, replicate it independently of the cell’s nuclear DNA, and have their own ribosomes for making proteins. Those ribosomes are more similar to bacterial ribosomes than to the ribosomes floating in the cytoplasm of the eukaryotic cell they live in.12PubMed Central. The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System Even the DNA repair system used in mitochondria shares features with the bacterial version rather than the eukaryotic nuclear one.
Over evolutionary time, the process of endosymbiotic gene transfer moved most of the original bacterial genes into the host cell’s nucleus, while co-evolving a specialized protein import system to shuttle the resulting proteins back into the mitochondrion where they were needed.13PubMed Central. Tracing the evolutionary pathway: on the origin of mitochondria and eukaryogenesis This arrangement means that today’s mitochondria depend on the nucleus for the vast majority of their proteins but still maintain a small essential genome of their own. That retained genome is what allows them to keep local control over oxidative phosphorylation, the energy-generating process at the inner membrane.
When Antibiotics Hit Mitochondria
The bacterial resemblance of mitochondria has a practical side effect that most people never think about. Many antibiotics work by targeting bacterial ribosomes or other features of bacterial cells, and because mitochondria share those features, some antibiotics inadvertently damage mitochondrial function. The toxicity of certain antibiotics is partly due to their interaction with mitochondria, because the organelle’s translation machinery retains key similarities to its bacterial counterpart.14PubMed. Side effects of antibiotics and perturbations of mitochondria functions
Not all classes of antibiotics are equally guilty. One study found that oxazolidinones, chloramphenicol, and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis, while macrolides, lincosamides, and aminoglycosides were not.15PubMed Central. Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones Aminoglycosides, though, appear to interact with mitochondrial ribosomes in other ways: research has shown that the binding affinities of aminoglycosides for a key structural element of human mitochondrial ribosomes are similar to those for the equivalent bacterial structure, which may help explain some of the well-known ototoxicity and kidney damage associated with that drug class.16PubMed Central. Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity The takeaway is that the evolutionary link between mitochondria and bacteria is not abstract biology. It is a factor that drug developers and clinicians have to account for when designing and prescribing antibiotics.
Do Prokaryotes Have Any Internal Compartments?
The blanket statement that prokaryotes lack internal organelles is true as a general rule, but biology is messy. Some bacteria have evolved internal structures that, while not mitochondria, blur the line between “simple” prokaryote and “complex” eukaryote.
The best-studied examples are bacterial microcompartments. These are self-assembling structures made entirely of protein, with no lipid membrane. Thousands of shell proteins form a polyhedral capsule that encapsulates enzymes for specific metabolic reactions.17PubMed Central. Evolutionary relationships among shell proteins of carboxysomes and metabolosomes The shells act like a protein cage, concentrating certain chemical pathways and keeping toxic intermediates contained.18PubMed Central. The protein shells of bacterial microcompartment organelles Carboxysomes, which help cyanobacteria fix carbon dioxide, are one well-known type. Other microcompartments handle reactions involving volatile or dangerous small molecules that the cell needs to keep sealed away from the rest of the cytoplasm.19PubMed Central. Bacterial microcompartment organelles: protein shell structure and evolution These compartments are functionally analogous to organelles in the sense that they create a distinct internal environment, but they are fundamentally different from mitochondria because they lack a lipid bilayer membrane and their own genome.
Then there are the Planctomycetes, a phylum of bacteria that have long fascinated cell biologists because their internal architecture looks unusually complex. Advanced imaging and proteomic analyses have revealed that Planctomycetes follow an altered version of the typical bacterial cell plan, including a defined outer membrane, a periplasmic space that can be greatly enlarged and convoluted, and an energized cytoplasmic membrane.20PubMed Central. Determining the bacterial cell biology of Planctomycetes Earlier researchers mistakenly interpreted some of these internal membranes as being analogous to a nucleus, but the current consensus is that Planctomycetes are genuinely Gram-negative bacteria with an unusually folded inner membrane system rather than true eukaryotic-style compartments.
A Giant Bacterium That Challenges the Rules
Perhaps the most spectacular recent challenge to the idea that prokaryotes must be simple came from Thiomargarita magnifica, a bacterium discovered in mangrove swamp sediments that can grow over a centimeter long, visible to the naked eye. This organism exceeds theoretical size limits for bacteria by orders of magnitude and does something no other known prokaryote does: it segregates its DNA and ribosomes into membrane-bound compartments that are metabolically active.21PubMed. A centimeter-long bacterium with DNA contained in metabolically active, membrane-bound organelles It also carries more than half a million copies of its genome, a level of polyploidy that dwarfs anything previously known in bacteria.
These internal compartments are not mitochondria. They do not appear to perform oxidative phosphorylation or have a separate genome from the rest of the cell. But their existence shows that at least one prokaryotic lineage has independently evolved membrane-bound organelles for organizing its genetic material, a trait previously considered exclusive to eukaryotes. T. magnifica is a reminder that the boundary between prokaryotic and eukaryotic cell organization, while real, is not as absolute as textbooks have traditionally implied.
Can a Eukaryote Lose Its Mitochondria?
If mitochondria are supposed to be essential to eukaryotic life, you might expect every eukaryotic cell to have them. Almost all do, but there is one known exception. Monocercomonoides exilis, a tiny single-celled organism that lives inside the guts of chinchillas, is the only known eukaryote to have completely lost its mitochondria and all associated proteins.22Open Biology. A mitochondrion-free eukaryote contains proteins capable of import into an exogenous mitochondrion-related organelle Its closest free-living relatives still have mitochondrial remnants, so the loss in Monocercomonoides was secondary: its ancestors once had mitochondria and gradually shed them.23Current Biology. An Oxymonad Eukaryote without Mitochondria
How did it survive? One key was replacing the mitochondrial iron-sulfur cluster assembly pathway, which is one of the few mitochondrial functions considered truly indispensable across eukaryotes. Monocercomonoides acquired an alternative system, called the SUF system, through horizontal gene transfer from bacteria. This bacterial replacement allowed it to bypass the last remaining essential function of the organelle and ultimately discard it entirely. The discovery of Monocercomonoides was significant because it showed that while mitochondria were necessary for eukaryotes to evolve, they are not strictly necessary for all eukaryotes to continue surviving, provided the right alternative systems are in place. That said, every other known eukaryote retains at least some form of mitochondrial remnant, so Monocercomonoides is genuinely exceptional rather than representative of a broader trend.
Recreating Endosymbiosis in the Lab
If the original endosymbiosis between a bacterium and an archaeal host cell gave rise to all complex life, can scientists recreate something similar in the lab? Researchers have begun trying. In one experiment, bacteria were injected directly into the cytoplasm of mammalian cells using a microscale injection technology. Among several bacterial species tested, E. coli grew exponentially inside the host cells, but too fast: its growth outpaced the host and killed it.24PubMed Central. Engineering Endosymbiotic Growth of E. coli in Mammalian Cells By engineering the E. coli to require amino acids it could not make on its own, the researchers slowed its intracellular growth enough to prolong survival of the host-endosymbiont pair.
This is obviously a far cry from the stable, vertically inherited partnership that mitochondria represent, which took hundreds of millions of years of co-evolution to refine. But the work provides a starting point for studying how two cells begin to negotiate the early stages of an endosymbiotic relationship, including the fundamental problem of controlling the guest’s growth rate. The original mitochondrial ancestor faced the same challenge: too aggressive, and it kills the host; too slow, and it offers no selective advantage. Understanding how nature solved that balance could have applications ranging from synthetic biology to the design of novel cellular therapies.