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Engineering Language Enters Biology — The Case of the Endosome

Photo credit: ThisisEngineering RAEng, via Unsplash.

Design advocates can welcome research that mentions engineering and ignores Darwinism. Biological research papers have for some time now used the word “orchestrated” to describe complex processes in the cell. Another word, though similar, conveys more clarity about the design implications: “engineered.” That word appeared recently in the journal Science under the title, “The Endosome as Engineer.” It was written by Maria Clara Zanellati and Sarah Cohen, cell biologists at the University of North Carolina.

The take-home lesson could be stated: If parts of a cell can re-engineer other parts for function, without which action the cell would die, and if the process involves signal communication between multiple other parts, what does that imply about the origin of the system? Can undirected mindless processes create engineers? Or does an automated engineering system presuppose a designer with foresight and a mind that understands how to make things work?

Zanellati and Cohen begin,

There has been increasing interest in organelle communication at membrane contact sites — where two organelles are anchored in close apposition by “tether” proteins. These contact sites allow the exchange of materials and information between cellular compartments. Intriguingly, organelles can also influence one another’s abundance and morphology. Most studies have focused on the role of the endoplasmic reticulum (ER) in shaping other organelles. However, on page 1188 of this issue, Jang et al. show that the endosome can reengineer ER shape in response to changing nutrient levels, which in turn affects the morphology and function of additional organelles. [Emphasis added.]

The paper by Jang et al., written by 11 scientists primarily from the Leibniz Institute in Berlin, investigated complex responses to nutrient starvation in muscle cells. The names of molecular players in this multi-part automatic response may be unfamiliar except for three key players explained below, but the upshot of the process is described as follows:

A cell can sense when it is getting starved for nutrients. When this happens, the powerhouses of the cell (the mitochondria) should not be allowed to carry on as if everything is fine, lest the cell go into self-destruction mode (autophagy). Distinct proteins fly into action, rewiring connections and preserving the powerhouses until conditions improve. One way they do this is by changing the shape of the ER from a tubular form to a sheet form.

Key Players in the Response

Here are the key players in this engineered response:

Mitochondria: The cell’s powerhouses, essential eukaryotic organelles where energy is produced via ATP synthase rotary engines. In “fed” conditions, mitochondria routinely undergo fusion and fission dynamically. The tubular ER membrane promotes genesis of lipid droplets that serve as a backup energy source for the mitochondria. In starvation conditions, “mitochondria fuse into tubular networks. This protects mitochondria from degradation by mitophagy and enables a metabolic shift to fatty acid oxidation.”

Endoplasmic Reticulum (ER): The cell’s central manufacturing and distribution center for proteins and lipids. As “the largest source of membrane in the cell and a major site of protein and lipid synthesis, the ER can act as a central node to convey environmental cues and exert effects on the growth and division of other organelles.” In starvation conditions, the ER changes shape. “The resulting loss of peripheral ER tubules induces mitochondrial network formation and the delivery of fatty acids to mitochondria to sustain cellular energy supply.”

Endosome: a package of nutrients sent from outside the cell to the ER. Endosomes in muscle cells contain a nutrient sensor. This sensor recruits “tether” proteins that bind the endosome along the microtubules in the ER, promoting fission of the mitochondria and lipid droplet formation (learn about droplets and other membraneless organelles here and here).

Shape-Shifting Automatic Response

If the nutrient sensor detects starvation, it recruits proteins that disassemble the sensors within the endosomes. This breaks the “tethers” to the transport proteins. The ER tubules change shape into sheets encompassing the mitochondria, stopping their fission delivering fatty acids to them.

The authors note that a failure in this system leads to a muscular disease that can be fatal. This indicates irreducible complexity, because a failure in any of the proteins and organelles involved leads to cell death, muscle failure, and potentially death to the organism.

From Engineered Instance to Engineered Cell

This shape-shifting strategy of organelles, mediated by sensor proteins, may be one example of a whole category of cellular systems now being discovered. The key finding in this research on the starvation response in the ER is that one organelle can change the shape of another organelle, altering its activity. As shown in the passage quoted above, Zanellati and Cohen expect other cases will be found now that organelles are often observed to be in contact or tethered to one another via threadlike proteins that exchange materials and information.

Membrane contact sites mediate the exchange of lipids, ions, and proteins between organelles. The first hint that organelles can influence one another’s morphology came from movies showing ER tubules wrapped around mitochondria at sites where the mitochondria divided. Mitochondria undergo constant fusion and fission. Fission can be associated with mitochondrial biogenesis needed for cell proliferation, or it can be a mechanism to degrade damaged pieces of mitochondria. Although cytoplasmic proteins were known to affect mitochondrial fission, it was surprising to discover that the ER regulates this process. 

Engineered morphological modification and communication between organelles could be a ubiquitous feature within cells. They conclude,

In addition to modulating mitochondrial fission, ER tubules regulate endosome fission. Thus, endosomal effects on ER morphology could feed back onto the morphology of endosomes themselves. The ER is a central hub of organelle communication. However, endosomal signaling lipids have been identified as an important mechanism for engineering ER shape, which relays nutrient information to distant mitochondria and lipid droplets.

Engineering Doesn’t Just Happen

Inanimate objects do not reengineer one another for function. Engineering, as one of the principal examples of mental activity in our culture, must be learned and taught by those who understand it. The regress of causality for engineering does not terminate downward to blind, unguided nature. In every case we know, it regresses upward to genius. Scientists doing pure research discovered the principles by which things work through laborious experimentation (exemplified by Faraday), and through mental prowess encapsulating them into theories (exemplified by the work of Maxwell), which were turned into practical applications (exemplified by Lord Kelvin, Marconi, and many others). From the giants of engineering, textbooks were written and taught to millions of students who continue to apply the design principles to projects that enrich our lives. The “phylogeny” of the tree of engineering traces back to a root of mind.

What, then, shall we think of microscopic systems in living cells that utilize engineering principles with finesse, which often keep an organism like Your Designed Body running for a century or more? Is it any surprise that none of the authors of the research described here made any reference to Darwin, evolution, ancestry, beneficial mutations, or natural selection? As Neil Thomas wrote recently, 

Natural selection reveals itself as not just a metaphor but a mixed one: Nature being dumb but nevertheless capable of discrimination. It is a poetic concept rather than a scientific one, appealing more to emotional and aesthetic sensibilities than to reason.

Some engineers may enjoy poetry as an avocation, but when at work must subjugate their aesthetic sensibilities to reasoning about realities. They must learn to apply scientific principles discovered by theoreticians and experimentalists to practical situations involving interacting parts. Life can serve as an example and a motivation, but in both life and engineering, function doesn’t emerge without intelligence.