One of the most recent GEITP chats concerned the “possibility that genes talk to one another,” and the “likelihood that cells in any tissue talk to one another.” This editorial article [attached] is a semi-layman’s story about subcellular organelles (various structures in cytoplasm and outside nucleus, inside each individual cell) that appear to be in constant communication with one another. In the 1950s, microscopists’ photographs showed mitochondria (energy-producing factories in cytoplasm) in close contact with the endoplasmic reticulum (ER; network of membranous tubules, continuous with the nuclear membrane; usually with ribosomes attached; involved in protein and lipid synthesis). Between the 1960s and 1980s, others noticed ER in close contact with the Golgi apparatus (complex of vesicles and folded membranes within the cytoplasm of most eukaryotic cells, involved in secretion and intracellular transport) and with the plasma membrane (outside wall of each cell). Yet, between 1950 and 1990, few perceived these contacts as something that might promote intracellular communication.
Starting in the 1990s, researchers began to focus on specific proteins — called tethers — that form contact points between organelles. In 2oo9, scientists identified a group of four proteins that collectively formed a tether between ER and mitochondria
in yeast cells. Deleting any one of the four proteins caused the tether to fail — resulting in defects in lipid exchange, as well as slower cell growth. In 2o12, researchers identified six tethering components, any one of which could correctly hold the tether together; the bond could be disrupted only by eliminating all six proteins. At first, all interactions seemed to involve ER, but then scientists began to document other connectors; and they soon realized that cells can re-route transport when “direct shipping lanes” are blocked.
In 2o13, scientists classified a “contact zone” containing at least two tethers and three organelles — ER, mitochondria and plasma membrane. Communication pathways have now been discovered that transmit cholesterol, oily waxes, and other fatty molecules; without proper transport out of the cell, these molecules would form fatty beads in the water-loving (hydrophilic) cytoplasm, plugging up the cell (much like ‘bacon grease in a drainpipe’). Calcium, hydrogen peroxide, and other water-soluble compounds are now realized also to flow through these portals — which helps the cell to aggregate these molecules for specific reactions.
Finally, specific human genetic diseases are being discovered that exhibit defects within this intracellular communication matrix.
“Mitochondrial stress”, “ER stress”, insulin resistance, diabetes, obesity, Charcot–Marie–Tooth disease (a rare degenerative nerve disorder), and some inherited cases of amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease) and Alzheimer disease — are examples of some of these disorders. From ER to the Golgi to vacuoles to endosomes, each organelle is still shown (in most textbooks) in isolation, rather than appreciating the tethers that contribute to a dynamic interactive communication system.
Nature 14 Mar 2o19; 567: 162-164