We tend to think of our cells as big blobby things.
But floating around the inside of our cells, is cell cycle machinery constantly regulating growth and repair signals.
One organelle called the lysosome acts like a tiny garbage can, a small membrane bound sac containing highly acidic degradative enzymes inside the cytoplasm. Lysosomes can inform the rest of the cell of its intracellular and extracellular milieu, and trigger pathways to help the cell adapt to emerging conditions.
Outfitted with pervasive sensing cilia and microtubules, the lysosome organelles are constantly sensing the microenvironment.
Now science is discovering that far from being passive, these lysosome organelles appear to signal inside out to the surface of the cell.
In the high tech world of Silicon Valley “pervasive sensing” is a familiar concept, and driving force behind today’s trends in automation as well as the Internet of Things (IoT). Robots equipped with sensors on the factory floor can for example send signals, alerting technicians that a damaged part needs repair.
The body may also come equipped with the biological equivalent of pervasive sensing equipment.
Sitting on the cell’s surface, microscopic cilia are tiny pervasive sensors that sense growth factors and nutrients. By activating an important growth pathway called the mechanistic target of rapamycin (mTOR), these tiny microtubule signals tell the cell when to get big, and divide.
A central regulator of human metabolism and physiology, the mTOR pathway is considered to be a major axis involved in aging. mTOR helps regulate the liver, muscle, adipose tissue, and the brain, and is dysregulated in diseases such as diabetes and certain cancers.
mTOR works closely with lysosomes, the small vesicles that help our cells take out the trash. Signals travel between the mTOR growth axis and our cells via a mechanism or signaling pathway involving microtubules and cilia.
In lungs epithelial cells in the airway are ciliated with multiple motile cilia. Motile cilia make a swishing motion to move fluid or clear debris. The presence of cilia in the respiratory track is critical for normal lung function, and alterations in these motile cilia contribute to the development of pathologies such as chronic bronchitis, or Acute Respiratory Distress Syndrome (ARDS).
But there’s also another type of cilia called immobile cilium. While we may be less familiar with these cilia their signals may be important. According to Dr. Jon Lieff, author of “The Secret Language of Cells”, although first observed in 1887 these primary or immobile cilia have been difficult to study because they are ten thousand times smaller than a human cell.
Scientists believe that these immobile cilia sit on the surface of cells, and can act as nutrient-sensing antennas. When amino acids and sugars are present in the blood stream, the cilia senses the exterior environment and knows that it is safe for the cell to divide. If nutrients are scarce, the cilia can signal to the cell to switch into a quiescent mode, stop dividing and growing, and instead focus on repair.
Inside the cell, the lysosome serves as a platform to assemble signaling hubs, on its surface. An aging pathway, the hormone axis mTORC1 uses the lysosome garbage can as a docking station, to lock on to and activate growth.
If sufficiently low levels of growth signals are present, and if mTOR is deactivated and undocked, the lysosome will signal to the cell to “switch on” autophagy or self-eating. In this quiescent or standby mode, autophagy is used to repair damaged components like misfolded proteins or defective mitochondria.
The mechanistic target of rapamycin (mTOR) pathway regulates cell growth and enlargement, and has been found to be aberrant in a wide variety of malignancies.
Scientists are now learning that more than acting as a passive blobby garbage can, the lysosome is more like a command center mTOR docking station sending signals to the cells’ surface antennae. Acting as a central processing unit of the cell, the lysosome triggers microtubules to grow.
Nutrients (proteins and sugars) are players in delivering a “go-no go” signal to the mTOR complex to be activated, and dock onto the lysosome. This cell cycle machinery can be observed in a video of fluorescent died lysosomes that move from the cytoplasm onto the lysosome or garbage can membrane wall.
When nutrients are scarce, autophagy delivers cytoplasmic cargo to lysosomes rather than extracellular cargo. Generally, surplus organelles, damaged organelles, protein aggregates, and free bacteria that escape phagosomes are targeted for autophagy.
In a catabolic state (when nutrients are scarce) mTOR will undock itself from the lysosome’s outer membrane. mTOR is deactivated by sensing a lack of amino acids such as leucine in the bloodstream.
Once dismissed as garbage cans, these tiny organelle lysosomes appear to be integrating extracellular signaling important to healthy cell cycle, and metabolism.
Autophagy, ketogenic diets, and measuring telomeres has grabbed headlines as a way to maintain health.
But the lysosome acting as a central processing unit coordinating healthy cilia signals may play an underlying role, regulated by nutrition.
Something as innocuous as protein and type of protein consumed in the diet could control when mTOR finds the “off” switch, to signal the body to switch to repair.
“Pile on the protein” is popular nutrition advice given to patients.
Eating to maintain muscle keeps the body strong and yet the molecular science cells a different story.
Scientists studying the mTOR complex point out that nutrient-sensing cilia vital to regulating homeostasis appear to be highly attuned to levels of protein in the bloodstream. Acting as tiny antennae cilia signals are constantly sensing the microenvironment and use nutrition (especially certain proteins) as an”on” and “off” switch for repair.
Like motile cilia in the lung that constantly clear out debris, these immobile cilia appear to be active players in health. How to keep cell cycle machinery working and protein’s role, may warrant further investigation.