Autophagy helps keep cells healthy. It can occur during sleep and other periods of short-term fasting, or be triggered by some medications.
This article explains the four steps of autophagy, its benefits, and what occurs when this process malfunctions.
Function
Autophagy has important effects that occur both within and outside of a cell.
Within the cell, autophagy can help:
Decrease oxidative stress, or stress on the body caused by unstable molecules (free radicals) that can damage cells Keep genes stable Improve conversion of nutrients into energy Increase the elimination of waste
Outside of the cell, autophagy may help to:
Decrease inflammation Improve balance of the neuroendocrine system, which involves hormonal substances influencing the activity of nerves Support detection of cancer by the immune system Increase the elimination of aging cells
A cell’s capacity to be broken down into parts through autophagy is believed to decline with age, contributing to the aging process.
Conditions that disrupt normal processes of autophagy can lead to chronic illness.
How Autophagy Works
Cytoplasm is the fluid inside of a cell. During autophagy, cytoplasm and organelles—small structures with specific functions—are recycled.
This process keeps your body in balance, or homeostasis, by self-removing parts of cells that are no longer functioning well.
Autophagy is typically triggered by a cell’s starvation of nutrients. This involves insulin and glucagon, hormones produced by the pancreas that are important in regulating blood sugar levels.
After eating, your body releases insulin, while fasting causes a release of glucagon as your blood sugar starts to decrease. Glucagon signals your body to use glycogen in your liver to increase your blood sugar.
It is believed that insulin suppresses autophagy while glucagon can activate the process.
Autophagy Cycles
Once autophagy is activated, the process occurs in four steps: sequestration, transport, degradation, and utilization.
The processes of autophagy are all important in maintaining balance. At any given point, any one or all of them may be used to meet the needs of the body.
Sequestration
During this step, two membranes called phagophores stretch around and eventually enclose cytoplasm and organelles that will later be broken down.
This double-membrane becomes an organelle known as an autophagosome.
Typically, the contents that make their way inside an autophagosome are selected because they are within range. However, autophagosomes can be selective and start autophagy when there is interaction with certain proteins in the cell.
Transport
A lysosome is a sac-like organelle that contains enzymes, proteins that trigger biological processes. These can be used in the breakdown process.
The autophagosomes cannot directly connect to a lysosome, so they first join with a go-between structure called an endosome. The result is called an amphisome, and it can readily join with a lysosome.
Degradation
Breakdown, known as degradation, can begin after this fusion occurs.
Upon connection with the amphisome, the lysosome releases enzymes known as hydrolases. The hydrolases degrade the materials that were in the original autophagosome.
This structure that is full of broken-down cellular material (amino acids) is now known as either an autolysosome or an autophagolysosome.
Utilization
After being exported out of the autolysosome and into the cellular fluid, the amino acids can then be reused.
This stage is ultimately related to the starvation of cellular nutrients.
The use of broken-down products is ultimately needed by amino acids for gluconeogenesis, a process in which the body forms glucose, or sugar, from non-carbohydrate sources.
The amino acids serve as an energy source for what’s called the tricarboxylic acid (TCA) cycle, which is when they are recycled to form new proteins.
Types
So far, this article has described macroautophagy, which is the main type of autophagy. The terms autophagy and macroautophagy can be used interchangeably.
But there are also two additional types:
Microautophagy is similar to macroautophagy except it does not use a phagophore. Instead, the lysosome draws the cellular contents in so it can break down the contents into amino acids for reuse. Chaperone-mediated autophagy is a more specific method of targeting proteins to be degraded. Chaperone proteins bind to other proteins to assist in folding, a cellular process that turns them into a three-dimensional shape so that they can function properly. As their name suggests, chaperone proteins also collect these other proteins and help transfer them across the lysosome membrane, where they can be degraded into amino acids for reuse.
Significance
Autophagy has many potential health benefits. As such, there is a lot of research dedicated to methods to activate this process.
In particular, there is interest in identifying ways to stimulate autophagy to help with neurodegenerative disorders, which damage cells and nervous system connections, as well as suppress autophagy in those with cancer.
The prospect of influencing autophagy also appeals to many people because of autophagy’s potential anti-aging properties and increased metabolic effects (namely, the breakdown and use of food as energy).
Neurodegenerative Disorder Drugs
The future of autophagy to treat disease may be promising. Researchers are trying to identify ways to selectively turn autophagy on or off with certain drugs.
Some neurodegenerative disorders like Parkinson’s disease have genetic links related to autophagy dysfunction.
Drugs are being investigated to see if they can stimulate autophagy in people with the following conditions:
Huntington’s disease Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis (ALS)
Cancer Treatment
Cancer is also related to abnormal autophagy, but not because of genes.
Autophagy has cell-protective properties that try to prevent cancers from forming. However, once a tumor is established, autophagy is believed to help protect the tumor from being destroyed by normal processes your body has to fight cancer.
Possible cancer therapies being investigated to inhibit autophagy target the lysosome portion of the process.
Fasting
Going without food either on and off (intermittently) or for more prolonged periods of time can induce autophagy.
It does this by depleting cellular nutrients. Autophagy is then triggered to produce amino acids that can be used as an energy source in order to maintain cellular function.
Most fasting research is limited to animal studies, so it’s still unclear what duration and frequency of fasting may be helpful or harmful in humans. It’s also uncertain if it can actually be used to help extend someone’s lifespan or help prevent or treat certain conditions.
For example, animal studies suggest that fasting may be helpful as a complement to cancer treatments, such as chemotherapy, in order to protect normal cells and potentially make it more effective. However, studies are needed to see if these results apply to humans.
So far, preliminary research suggests that short-term fasting during chemotherapy treatment is typically safe for people, though challenging.
In addition to fasting, diets that involve low carbohydrate intake deprive the body of easy-to-access sugars. Autophagy may be activated to participate in the generation of amino acids, which can then be used to provide energy through gluconeogenesis and the TCA cycle since carbohydrates are not readily available.
Associated Conditions
Autophagy-related genes (ATG) were first identified in the 1990s.
Since that time, ATGs have been linked to many disorders, especially neurodegenerative disorders.
Some of the disorders related to abnormal function of autophagy include:
Static encephalopathy of childhood with neurodegeneration in adulthood (SENDA): This neurodegenerative disorder leads to an accumulation of iron in the brain, developmental delays in childhood, and severe disability in adulthood. The gene associated with SENDA affects the formation of autophagosomes. Vici syndrome: This progressive neurodegenerative disorder is owed to a recessive gene. That means both parents have to pass it on for a child to be affected. The associated gene affects how autophagosomes mature and are degraded. Hereditary spastic paraparesis (also called hereditary spastic paraplegia) is another recessive gene disorder that is neurodegenerative and affects the lower limbs. While autophagy’s role is not fully understood, the associated gene impairs both the formation of autophagosomes and the fusion of the autophagosome with the lysosome. Parkinson’s disease is a neurodegenerative disorder and is affected differently than other disorders. In this case, the associated gene is believed to cause selective degradation of mitochondria (a cellular structure associated with the generation of energy) by autophagy. This is referred to as mitophagy. Crohn’s disease is an inflammatory bowel disorder. There are several genes known to affect autophagy as it relates to Crohn’s disease. However, these same genes are also related to many other processes. It is unclear if Crohn’s disease is an autophagy-related disorder and whether autophagy-targeted therapies would be viable treatment options.
SENDA was the first neurodegenerative disorder to be identified as being related to autophagy dysfunction. This became important in identifying autophagy’s role in the potential to treat other neurodegenerative disorders.
How autophagy dysfunction relates to the accumulation of brain iron in those with SENDA is still unknown.
Summary
Autophagy is a key process that keeps your body’s cells in proper balance by taking aged or damaged components in a cell and recycling them. The recycled parts are turned into amino acids that can be used for fuel or to form new proteins.
Autophagy dysfuction is genetically linked to certain neurodegenerative disorders that affect the nervous system and its connections.
Autophagy can help protect against cancer. But once a cancerous tumor gets established, it may actually protect the cancer cells in some cases.
Researchers are looking at ways that medication or lifestyle, such as fasting, may be used as supportive treatments that target autophagy.
A Word From Verywell
The study of autophagy is an emerging field that holds promise. There is still a lot to be learned.
Always consult a healthcare provider if you are planning to try fasting or other dietary shifts in order to encourage autophagy, especially if you have any chronic health conditions or are on any medications. They can best determine if it is safe for you and help ensure you still get proper nutrition.
