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Autophagy

Autophagy featured article

Introduction

Homeostasis, a cell's ability to maintain a constant internal environment, is essential to cell survival. It is predicated on achieving an equilibrium between the production and degradation of cellular components. One major pathway for degradation is autophagy, an intracellular program involved in the disassembly and recycling of unnecessary or dysfunctional cellular components.

Autophagy (pronounced "aw-TAW-fuh-jee"), or "self-eating," is a highly conserved adaptive response to stress. This ancient defense mechanism sequesters protein aggregates, pathogens, and damaged or dysfunctional organelles into vesicles – bubble-like structures inside the cell called autophagosomes – and then delivers them for destruction to release macromolecules such as proteins, fats, carbohydrates, and nucleic acids for energy and re-use. Autophagy's primary goal The primary goal is to allow the cell to adapt to changing conditions and external stressors.

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Episodes

exercise

The effect of vigorous exercise on fat oxidation and mitochondria | Dr. Martin Gibala

Posted on October 4th 2023 (over 1 year)

In this clip, Dr. Martin Gibala outlines the relationship between exercise types, mitochondrial growth, and their combined effect on fat metabolism.

autophagy

Autophagy and cancer: a crucial role in immunosurveillance and chemotherapeutic treatment

Posted on April 9th 2022 (about 3 years)

Autophagy plays a role in triggering mechanisms of immunosurveillance by facilitating the release of ATP from dying cells, which attract the attention of myeloid cells via a special class of receptor known as purinergic receptors.

fasting

The evolutionary origin of hormesis | Dr. Mark Mattson

Posted on April 2nd 2022 (about 3 years)

In this clip, Dr. Mark Mattson describes the importance of transient, short-term, mild energetic stress to maintain healthy cells.

Topic Pages

  • Autophagy

    Autophagy is a conserved catabolic pathway where double-membrane autophagosomes deliver cytoplasmic cargo to lysosomes for degradation.

  • Fasting

    Fasting-induced nutrient deprivation inhibits mTORC1, activates the ULK1 complex, thereby promoting macroautophagy-mediated intracellular component recycling.

News & Publications

  • Chronic stress inhibits autophagy—the brain's recycling system—but restoring its functionality yields rapid antidepressant effects. pubmed.ncbi.nlm.nih.gov
    Brain Depression Stress Autophagy

    In small doses, stress can sharpen focus and improve resilience, but chronic stress gradually erodes emotional stability, increasing the risk of major depressive disorder. A recent study found that autophagy—the brain’s recycling and housekeeping system—helps maintain emotional stability by removing old or damaged proteins.

    Researchers explored how short-term and long-term stress influenced autophagy in mice and investigated whether antidepressant drugs could restore this process. Employing genetic techniques, the researchers selectively inhibited or enhanced autophagy in a region of the brain called the lateral habenula and then monitored how the animals reacted to stress.

    They found that acute stress activated autophagy, while chronic stress inhibited it. When autophagy ceased functioning properly, stress-related behaviors increased. However, restoring autophagy—even briefly—produced rapid antidepressant-like effects. Drugs commonly used to treat depression also reactivated autophagy in this brain region. Additional experiments indicated that autophagy helps regulate brain cell activity by breaking down excess glutamate receptors, which are often overactive in depression.

    These findings suggest that disrupted autophagy in the lateral habenula plays a central role in how chronic stress contributes to depression. Learn more about autophagy in this episode featuring Dr. Guido Kroemer.

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  • Time-restricted eating activates genes involved in metabolism and autophagy. www.sciencedaily.com
    Metabolism Genetics Autophagy Time-Restricted Eating

    Time-restricted eating influences the activation of roughly 70 percent of all genes in mice, a new study shows. Mice that ate on a time-restricted schedule had fewer active genes involved in inflammation and oxidative stress and more active genes involved in metabolism and autophagy – a cellular defense mechanism.

    Researchers fed two groups of mice a Western-style diet, which is high in fat and sugars, for seven weeks. One group was allowed to eat whenever they chose to, but the other group was allowed to eat only during a nine-hour window each day. At the end of the seven-week intervention, the researchers analyzed gene activity in the animals' tissues at different times of the day.

    They found that time-restricted eating altered the activity of more than 80 percent of genes involved in protein synthesis, folding, and maintenance. They also found that time-restricted eating altered amino acid, fat, and glucose metabolism and re-aligned the circadian rhythms of the animals' organs.

    These findings suggest that time-restricted eating influences gene activity in mice. If the findings translate to humans, they could have far-reaching implications for chronic metabolic disorders, neurodegenerative diseases, cancer, and other diseases. Learn more about the health benefits of time-restricted eating in this episode featuring Dr. Satchin Panda, the senior investigator for this study.

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