Everything You Think You Know About Endosymbiosis is Wrong! (Maybe)

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One of the reasons I've been MIA lately is that I'm tutoring several students in biochemistry and cell biology.  I recently finished explaining the theory of endosymbiosis to one of my students.  That's the theory that explains the origin of eukaryotic cells - that is, mitochondria and chloroplasts, and possibly other organelles, represent formerly free-living prokaryotes that were ingested in another cell.  It is supported by the fact that these organelles are double-membraned, have their own DNA, and can replicate independently of the rest of the cell.  But now, a new open access meta-analysis has decided to shake this all up, stating that the origin of eukaryotic cells happened from the inside-out.

The origin of eukaryotic cells is recognized as the single most important change in cellular organization during the evolution of life, but for all its importance, we know very little about how it happened.  We know that the key events were the acquisition of the nucleus, the endomembrane system (which includes the endoplasmic reticulum, vesicles, and golgi), and the mitochondria.  I'm sure plants also consider the acquisition of a chloroplast as a pretty key event, but that is not the focus here.


Anyway, no one is disputing that mitochondria arose from the engulfing of aerobic prokaryotic cells.  But the authors here challenge the idea that the nucleus formed as a novel structure inside the existing cell, as a process of infolding of the plasma membrane.  The authors argue that, rather, the rest of the cell was formed from the extrusion of the plasma membrane.  Their major argument here is that it seems unlikely that a cell would have an infolding of the plasma membrane, AND THEN engulf a prokaryotic cell.  If we look at it using this "inside-out" theory, as the membrane protrusions started to surround the ancestral prokaryotic cell (now the nucleus), it also trapped anaerobic prokaryotes (proto-mitochondria), thus leading to the simultaneous development of the membrane-bound organelle system (left).

To support their theory, the authors first analyze the pieces:

What's the benefit in extracellular protrusions?
These protrusions (which biologists also like to call "blebs," because protrusions is a mouthful) arise to facilitate the exchange of materials with the environment.  This is something that is not seen in bacteria, but is commonly seen in Archaea, a kingdom of single-celled organisms that look like bacteria but are actually quite different at the molecular level.  It's still unclear how these protrusions are formed and stabilized, but some of the proteins that are potentially involved are the same ones that make up the structural components of the nuclear pore.  Further, proteins involved in maintaining the curvature of the endoplasmic reticulum may also be involved.

Selective pressure
Ok, so once the archaeon (singular form of archaea) has those protrusions, what selective pressure keeps them there?  Well, the authors suggest it may have been an increasingly intimate association with proto-mitochondria.

Same as the endosymbiotic theory, the cooperation of the cell and proto-mitochondria was mutually beneficial in this inside-out theory as well.  The aerobic prokaryote was able to provide the cell with all types of materials, potentially including hydrogen, sulfur, hydrogen sulfide, organic acids, and ATP (aka cellular energy).  This stays the same in both theories.  The only part that's different here is that instead of being engulfed by the larger cell, the proto-mitochondria interacted with the membrane protrusions, and just got swept in with the formation of the endomembrane system.

The authors also argue that it is unlikely that the aerobic prokaryote would have been engulfed, since engulfing food takes a lot of energy, and this energy is produced in the mitochondrion.  Looking at it that way, the endosymbiotic theory is a bit of a catch-22 - how did the cell get enough energy to engulf a proto-mitochondrion without a mitochondrion being present in the first place?

Syncytia is the term for multinucleated
cells formed during cell fusions.  This
is what it look like.  Source.

Essentially, the authors compare their theory to common-sense architecture.  You wouldn't build a building from the outside-in.  Rather, you might start with the "command center" and then add on to it as needed from the inside-out.  They also think that their theory helps to explain some previously enigmatic aspects of cell biology, like the autonomy of nuclei in multinucleated cells and the subcellular localization of protein N-glycosylation.

The authors also express their excitement for the field of cell biology because of this new theory.  They recognize that it's easy for students of cell biology to think they'll never make an impact in a field where almost everything is known.  But this new idea of theirs shows that there are still many mysteries when it comes to cell biology.  Not everyone will accept this theory, but it will encourage researchers to think about it, and to test it!