Biological complexity: cellular cleanup (Introduction)

by David Turell , Wednesday, February 08, 2023, 19:29 (654 days ago) @ David Turell

Regular garbage disposal:

https://phys.org/news/2023-02-cells-routinely-self-cannibalize-trash-aiding.html

"Since routine cellular activity generates toxic byproducts that can damage the cell, a disposal system is needed to degrade and recycle these molecules within cells. One of these processes is autophagy, a form of self-consumption cells use to eliminate and recycle abnormal or excess components, including proteins and organelles. Derived from Greek, the term literally translates to "self-eating." In 2016, cell biologist Yoshinori Ohsumi won the Nobel Prize in Physiology or Medicine for his work on autophagy. Autophagy is essential for cellular health and longevity. When this process is not working well, it's linked to several human diseases, including neurodegenerative and cardiovascular diseases and cancer.

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"...autophagy appears to play a paradoxical role in cancer. On one hand, some studies have shown that because this process suppresses tumors by eliminating potentially harmful material, reduced or impaired autophagy can turn a cell cancerous. On the other hand, activating autophagy after a tumor has formed can promote cancer by helping it adapt and survive, potentially leading to treatment resistance.

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"Dysfunctional autophagy also plays an important role in most neurodegenerative diseases. The aggregation of abnormal proteins in brain cells are common features in Alzheimer's disease, Parkinson's disease, Huntington's disease and ALS. Some scientists believe that the accumulation of these proteins is due at least in part to a decline in their degradation through autophagy.

"Autophagy is also important for heart health. Researchers have found that autophagy in the heart declines with age and contributes to cardiovascular disease. Decreased autophagy in cardiac muscle cells results in accumulating cellular garbage that can affect their ability to contract and even cause their death. With fewer cells and less contraction, the buildup of toxic material in cardiac muscle cells can ultimately lead to heart failure.

"For autophagy to be efficient, it needs to specifically get rid of only damaged proteins or organelles within the cell. Uncontrolled degradation would deprive a cell of its basic needs.

"This is particularly true for mitochondria, as cells rely on them for much of their energy production. Our team has been very interested in how cells ensure that autophagy of mitochondria, also known as mitophagy, eliminates only dysfunctional mitochondria while sparing the healthy parts of the cell. Dysfunctional mitophagy has been linked to cancer, neurodegeneration and cardiovascular disease, among other diseases.

"The process of autophagy starts when the cell begins to form a membrane near damaged proteins or organelles. This membrane will expand into a vesicle, or sac, known as an autophagosome, that engulfs the damaged material. It will then fuse with another internal cell structure full of acid called a lysosome that helps degrade its cargo.

"Beclin1 is a protein known to promote the formation of autophagosomes in cells. However, its role in mitophagy is controversial, in part because very little is known about its close relative Beclin2. We wanted to disentangle the functions of these two proteins and determine their role in mitophagy. To do this, we used mouse and human cell models to examine how the presence or absence of these two proteins affected autophagy.

"We discovered that activating a region unique to Beclin1 enables it to promote autophagosome formation next to dysfunctional mitochondria, facilitating their degradation in human cells. Because a similar region isn't found in Beclin2, this meant that only Beclin1 may be essential for mitophagy.

"Interestingly, we also observed Beclin1 at discrete points of contact between mitochondria and endoplasmic reticulum during mitophagy. This supports emerging research suggesting that physical interactions between these organelles facilitate the transfer of certain molecules needed to make autophagosomes. Our work indicates that only Beclin1 promotes engulfment of damaged mitochondria at these sites. Beclin2 may perform a different role in autophagy in other conditions."

Comment: another mechanism that had to be designed in toto when first cells appeared. If the cells couldn't clean up hey would not have survived. Irreducible complexity.
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