Cells have more mini ‘organs’ than researchers thought − unbound by membranes, these rogue organelles challenge biology’s fundamentals

Think about that basic biology class you took in high school. You’ve probably heard of organelles, the little “organs” inside cells that form compartments with individual functions. For example, mitochondria produce energy, lysosomes recycle waste, and the nucleus stores DNA. Although each organelle has a different function, they are similar in that each is enveloped in a membrane.

Membrane-bound organelles were the classic standard for how scientists thought cells were organized until they realized in the mid-2000s that some organelles didn’t need to be wrapped in a membrane. Since then, researchers have discovered many other membraneless organelles that have significantly changed the way biologists think about chemistry and the origins of life.

I discovered membraneless organelles, formerly called biomolecular condensates, a few years ago when students in my lab observed unusual spots in the nucleus of a cell. Unbeknownst to me, we had been studying biomolecular condensates for years. What I ultimately saw in these blobs opened my eyes to a whole new world of cell biology.

Like a lava lamp

To get an idea of ​​what a biomolecular condensate looks like, imagine a lava lamp where the wax drops inside merge, break apart, and merge again. Condensates form in much the same way, although they are not made of wax. Instead, a group of proteins and genetic material, particularly RNA molecules, in a cell condense into gel-like droplets.

Some proteins and RNAs do this because they preferentially interact with each other rather than with their environment, much like the way wax drops in a lava lamp mix with each other but not with the surrounding liquid. These condensates create a new microenvironment that attracts additional proteins and RNA molecules, forming a unique biochemical compartment within cells.

As of 2022, researchers have discovered about 30 types of these membrane-free biomolecular condensates. In comparison, there are about a dozen traditional membrane-bound organelles known.

Although they are easy to identify once you know what you are looking for, it is difficult to understand what exactly biomolecular condensates are used for. Some have well-defined roles, such as the formation of reproductive cells, stress granules, and protein-producing ribosomes. However, many others do not have clear functions.

Non-membrane-bound organelles may have more numerous and diverse functions than their membrane-bound counterparts. Learning about these unknown functions affects scientists’ fundamental understanding of how cells work.

Protein structure and function

Biomolecular condensates shatter some long-held beliefs about protein chemistry.

Since scientists first studied the structure of the myoglobin protein in the 1950s, it was clear that its structure was important to its ability to transport oxygen in muscles. Since then, the mantra of biochemists has been that the structure of proteins equals their function. Basically, proteins have certain shapes that allow them to do their job.

Proteins that form biomolecular condensates at least partially violate this rule since they contain disordered regions, that is, they do not have defined shapes. When researchers discovered these so-called intrinsically disordered proteins, or IDPs, in the early 1980s, they were initially confounded by the fact that these proteins could lack solid structure while still performing specific functions.

Later, they discovered that PDIs tended to form condensates. As is so often the case in science, this discovery solved one mystery about the roles these unstructured proteins play in the cell, only to open up another, deeper question about what biomolecular condensates actually are.

Bacterial cells

Researchers have also detected biomolecular condensates in prokaryotic or bacterial cells, which were traditionally defined as not containing organelles. This discovery could have profound effects on how scientists understand the biology of prokaryotic cells.

Only about 6% of bacterial proteins have disordered regions lacking structure, compared to 30 to 40% of eukaryotic or nonbacterial proteins. But scientists have discovered several biomolecular condensates in prokaryotic cells that participate in various cellular functions, including the manufacture and degradation of RNA.

The presence of biomolecular condensates in bacterial cells means that these microbes are not simple bags of proteins and nucleic acids, but are actually more complex than previously thought.

Origins of life

Biomolecular condensates are also changing the way scientists think about the origins of life on Earth.

There is ample evidence that nucleotides, the building blocks of RNA and DNA, can most likely be made from common chemicals, such as hydrogen cyanide and water, in the presence of common energy sources, such as ultraviolet light or high temperatures, on universally common minerals, such as silica and iron clay.

There is also evidence that individual nucleotides can spontaneously assemble into chains to produce RNA. This is a crucial step in the RNA world hypothesis, which posits that the first “life forms” on Earth were strands of RNA.

A major question is how these RNA molecules could have evolved mechanisms to replicate and organize themselves into a protocell. Since all known life is enclosed in membranes, researchers studying the origin of life have generally assumed that membranes should also encapsulate these RNAs. This would require synthesizing the lipids, or fats, that make up the membranes. However, the materials needed to make lipids were probably not present on the early Earth.

With the discovery that RNAs can spontaneously form biomolecular condensates, lipids would no longer be necessary to form protocells. If RNAs were capable of aggregating into biomolecular condensates on their own, it would become even more plausible that living molecules arose from non-living chemicals on Earth.

New treatments

For me and other scientists who study biomolecular condensates, it’s exciting to dream about how these rule-breaking entities will change our perspective on how biology works. Condensates are already changing our perception of human diseases like Alzheimer’s disease, Huntington’s disease and Lou Gehrig’s disease.

To this end, researchers are developing several new approaches to manipulate condensates for medical purposes, such as new drugs that can promote or dissolve condensates. It remains to be seen whether this new approach to treating diseases will bear fruit.

In the long term, I would not be surprised if each biomolecular condensate is ultimately assigned a particular function. If that happens, it’s a safe bet that high school biology students will have even more to learn — or complain about — in their introductory biology classes.

This article is republished from The Conversation, an independent, nonprofit news organization that brings you trusted facts and analysis to help you make sense of our complex world. It was written by: Allan Albig, Boise State University

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Allan Albig receives funding from the National Institute of Health.