Biological complexity: cellular organelles communicate (Introduction)

by David Turell @, Monday, March 11, 2019, 19:30 (15 days ago) @ David Turell

There is lots of cross talk and communication between all parts of the cells:

"In a 1990 paper, Vance showed that the meeting points between the ER and mitochondria were crucibles for the synthesis of lipids1. By bringing the two organelles together, these junctions could serve as portals for the transfer of newly made fats. This would answer the long-standing question of how mitochondria receive certain lipids — they are directly passed from the ER.


"close to three decades later, Vance’s paper is seen as a landmark — one that has come to transform scientists’ understanding of how cells maintain order and function in their crowded interiors, which buzz with various types of organelles, including mitochondria, nuclei and the ER. Researchers now recognize that interactions between organelles are ubiquitous, with almost every type coming into close conversation with every other type. Probing those connections is also leading biologists to discover proteins that are responsible for holding the organelles together and maintaining a healthy cell.


" Vance’s 1990 paper was seldom cited until the past decade, when the field rediscovered her work. That’s also when researchers began to pinpoint the specific proteins — called tethers — that form the contact points between organelles. Knowing their identity meant that cell biologists could artificially construct contact sites or destroy them and, in so doing, drill down into the function of the different trading exchanges.


"Scott Emr, a yeast biologist at Cornell University in Ithaca, New York, encountered this when he began studying contact sites between the ER and the plasma membrane. His group eventually identified six tethering components, any one of which could correctly hold the tether together4. His team could disrupt the bond only by eliminating all six proteins.

"The quest to identify tethers is also complicated by the elaborate network of interactions between organelles. At first, all interactions seemed to involve the ER. But scientists began to document other couplings. And they soon realized that cells can reroute transport when direct shipping lanes are blocked.


"Mitochondrial biologist Jodi Nunnari at the University of California, Davis, and her then colleague, cell biologist Laura Lackner, classified7 a super-contact zone containing at least two tethers and three organelles — the ER, mitochondria and the plasma membrane. “It really seems like this is some sort of functional hub that the cell has created,” says Lackner, now at Northwestern University in Evanston, Illinois. “It brings in a whole other layer of spatial organization.”


"One of the earliest functions to come to light was cargo transfer. After Vance’s initial discovery, experiments revealed that organelle contacts are almost like a gangway for exchanging goods between two ships. These sites transmit cholesterol, oily waxes and other fatty molecules that would otherwise form beads in the watery cytoplasmic sea, plugging up the cell like bacon grease in a drainpipe.

"Calcium, hydrogen peroxide and other water-soluble compounds also flow through these portals,
which helps the cell to aggregate these molecules for specific reactions.


"A few years later, Voeltz showed that a similar process also explains the division of organelles known as endosomes that help to sort and deliver molecular cargo10. Initially, she says, most scientists doubted that ER–endosome contacts even existed or were important. “Now it’s accepted as obvious,” Voeltz says


"the researchers identified dozens of proteins localized to contact sites: some served as tethers, but others were simply anchored in contact zones. “Most of them are completely unstudied,” says Schuldiner, hinting that these proteins might have other, undiscovered roles.


"As the evidence mounts that contact sites affect cellular function in both health and disease, some researchers have begun to talk about the need for a grand new synthesis of cellular transport. “An organelle cannot function in isolation,” Schuldiner says. And Lippincott-Schwartz sees an exciting future in cell biology: “This field of organelle–organelle communication and coupling is going to reveal really fundamental processes.”

"But there are still technical details to work out. Most research has focused on lipid or calcium shuttling between the ER and other organelles. The challenge now is to uncover the whole spectrum of signals transmitted across all contact sites."

Comment: All of this is automatic activity as the cell produces its products. A complex going factory. Huge article, hard to compress.

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