Autophagy fights disease through cellular self-digestion

Summary

This is the Nature review that brought autophagy to mainstream biomedical attention. Authored by four of the field's most prominent researchers — Mizushima, Beth Levine, Ana Maria Cuervo, and Daniel Klionsky — the paper synthesizes what was known by 2008 about cellular self-digestion as a regulated, disease-relevant process. The authors lay out three core ideas. First, autophagy operates at a basal level in all eukaryotic cells and can be induced by environmental stress — most notably nutrient deprivation, but also hormonal signals, hypoxia, and pathogens. Second, the regulatory pathway centers on mTOR (target of rapamycin), which inhibits autophagy when nutrients are abundant; when mTOR is suppressed (by fasting, by rapamycin, or by genetic loss of function), autophagy is unleashed. Third, autophagy plays both protective and harmful roles depending on context: it prevents neurodegeneration, fights infection, and clears damaged proteins, but cancer cells and some pathogens can hijack the process to survive. The review remains the foundational citation for almost any modern paper on autophagy's role in disease.