What Is Autophagy?

Autophagy Definition: Autophagy (from the Greek for self-eating) is the regulated process by which a cell degrades its dysfunctional or foreign components. The cell can then recycle useful chemical components for further purposes.

This allows autophagy to regulate the balance of protein composition in a cell, prevent the buildup of toxic waste products, maintain cellular organelle function, remove invading pathogens, and help sustain cells during periods of starvation.

The scientific importance of understanding autophagy was highlighted when the 2016 Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his discoveries of mechanisms for autophagy.

Essentially, autophagy is the creation of a ‘garbage bag’ (autophagosome) that collects cellular components and then takes them to the cell’s ‘recycling center’ (lysosome) to be broken down into their parts which can then be recycled into new components.

Autophagy-related genes (ATG) are responsible for creating the structures that carry out autophagy. The VPS34 complex initiates the autophagosome, ATG9 contributes to its expansion, and the ATG12-ATG5ATG16L1 complex recruits ATG8 proteins which complete formation and are involved in targeted capture.

Other genes are involved in turning autophagy on and off. In particular, genes that can detect changes in the cell. mTOR responds to the level of nutrients in a cell and decreases autophagy (by disrupting ULK1 preventing the formation of the VPS34 complex) when there are plenty of nutrients available. AMPK monitors the energy levels in a cell (the amount of ATP) and activates autophagy when they are low. HIF1A detects oxygen levels and turns on autophagy (targeting mitochondria) when they are low (hypoxia) .

Sirtuin genes (activated by resveratrol) can inhibit mTOR which increases autophagy [6]. Low levels of NAD+ are also reported to increase autophagy [7].

The Benefits of Autophagy

When things are running smoothly in a cell, autophagy occurs at a low level, helping to recycle worn-out cellular components. It’s a type of ‘maintenance’ mode.

But when things become stressed in a cell (not enough nutrients or energy, dysfunctional components, or invasion by microbes), autophagy is turned up in order to help protect us. A ‘stress response’ mode.

Can Extend Lifespans

Activation of autophagy counteracts the age-associated accumulation of damaged cellular components and enhances the metabolic efficiency of cells.

Autophagy is a response to stress that helps cells to become more resilient and conservative with their energy.

In particular, autophagy can be activated to remove dysfunctional mitochondria (mitophagy) which produce a lot of harmful reactive oxygen species (ROS) that degrade the cell .

These processes are reported to extend the lifespan of several species .

Protects Against Psychiatric Disorders

Typical functioning of autophagy provides protection against the development of psychiatric disorders. Disruptions to autophagic processes have been associated with increased risk for some psychiatric conditions.

Post-mortem studies of the brains of individuals with depression and schizophrenia identified deficiencies in essential autophagy pathways .

Prevents Neurodegenerative Disorders

Many neurodegenerative disorders stem from the accumulation of deformed proteins in and around neurons, inducing gradual brain cell death and subsequent loss of mental faculties .

Autophagy protects us by removing these proteins.

In Huntington’s disease it removes the huntingtin (HTT) protein , in Alzheimer’s disease it removes amyloid ꞵ (created from the APP protein) , in Parkinson’s disease it removes ⍺-synuclein (SNCA), and in dementia it removes microtubule-associated protein tau (MAPT) .

Helps Fight Against Infectious Diseases

Autophagy contributes to fighting infectious diseases in three ways;

  1. Direct removal of microbes from inside of cells (xenophagy)
  2. Removal of toxins created by infections
  3. Modulation of the immune response to infections

Infectious microbes such as Mycobacterium tuberculosis and the Group A Streptococcus, along with viruses such as HIV and protozoans are removed by autophagy .

Helps to Regulate Inflammation

Autophagy can both increase and decrease inflammation responses within the body.

It increases inflammation by presenting evidence of pathogen invasion and turning on the immune response.

Autophagy then decreases the inflammation brought about by an immune response by clearing the cell of antigens that are stimulating the response. Additionally, autophagy also removes pro-immune response molecules produced by the cell in response to an invasion .

Improves Muscle Performance

When exercising we place stress on our cells. Energy use goes up and components get worn out faster.

Autophagy is increased in response to this in order to:

  • maintain energy use balance within the cell
  • reduce the amount of external energy required (by more efficiently recycling existing energy molecules)
  • ensure that degraded cellular components are removed before they begin to cause any trouble

Involved in Cancer Prevention

Autophagy plays a role in preventing the onset of cancer and inhibiting the growth of early-stage cancers.

Autophagy suppresses pro-cancer processes such as chronic inflammation, DNA damage response, and genome instability .

Mice genetically engineered to have impaired autophagy are reported to have increased rates of cancer .

Unfortunately, the protective roles of autophagy may also be harnessed by cancerous cells within tumors.