Targeting "little brother" of cell death

Cellular self-cleaning mechanism is riddled

Autophagy vesicles in action Klionsky and Rafferty
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The cells of all higher organisms have an internal mechanism to break down or recycle parts of themselves. This process, also known as autophagy, has only recently been discovered. Whether this self-cleaning harms or protects the cells is still unclear - but could prove crucial for the development and research of cancer and other diseases.

Today, autophagy, in addition to apoptosis, is considered the second form of programmed cell death and a similarly promising starting point for possible therapies. The journal Science therefore dedicates its title to this field of research in the current issue. More recently, many organisms have identified genes that control autophagy, while also recognizing some of the environmental factors that can trigger the process.

Good or bad?

However, the current findings do not allow a clear conclusion about whether the autophagy is good or bad for the cell and the entire organism. "It could also be both, depending on when it takes place, " explains Daniel Klionsky, Professor of Molecular and Developmental Biology at the University of Michigan. "Autophagy is the only way for the cell to get rid of damaged components without destroying the entire cell."

During autophagy, the cell produces tiny bubbles, vesicles that envelop and dissolve the expendable cell building blocks. Autophagic vesicles have also been observed in cells during apoptosis, but researchers have not been able to determine whether the vesicles act against cell death or accelerate destruction. Also in some forms of degenerative muscle and nerve diseases such as ALS, Huntington's chorea, Parkinson's or Alzheimer's accumulations of such vesicles have been found. But even here it is unclear whether the bubbles accumulate because they are not needed or because the stressed cells build more vesicles.

Cancer: Prevents but protects tumor cells?

"Before the genes for autophagy in yeast were identified, the entire area was at its wit's end, " explains Klionsky. Now, researchers can detect autophagy genes in mice, humans, and other organisms and selectively alter their regulation to explore their mode of action. display

Cancer researchers in particular have long been searching for a way to transform programmed cell death into a kind of suicide program for cancer cells. Control of autophagy may prove equally effective. "If you could turn it on and off as you wish, it could be used as a therapy, " says Klionsky. Autophagy acts as a tumor suppressor by limiting cell size and removing damaged building blocks that could generate free radicals or genetic mutations. A study in mice with suppressed autophagy showed that the animals had a higher rate of spontaneous tumor formation. But at the same time, it could also protect cancer cells against some forms of therapy by extending their lifespan by recycling cell building blocks.

Antivirus and fountain of youth

Even with infections, autophagy seems to be useful for the organism because it can remove invading viruses and bacteria from the affected cells. However, some pathogens are armed and have developed special genes that block autophagy. Autophagy may even prove to be a "fountain of youth". Experiments with the roundworm Caenorhabditis elegans have shown that a blocked autophagy significantly reduced the lifespan of the animals. "This is a really hot field of research right now, " explains Klionsky. "We have a lot of really interesting questions to answer about autophagy."

(University of Michigan, 10.11.2004 - NPO)