From Christian de Duve to Yoshinori Ohsumi : more to autophagy than just dining at home

Harnett, Margaret M. and Pineda, Miguel and Latré de Laté, Perle and Eason, Russell J. and Besteiro, Sébastien and Harnett, William and Langsley, Gordon (2017) From Christian de Duve to Yoshinori Ohsumi : more to autophagy than just dining at home. Biomedical Journal, 40 (1). pp. 9-22. ISSN 2320-2890

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    Abstract

    The word « autophagy » stems from the Greek words “auto and phagy” meaning “self-eating” and it refers to degradation (eating) of a cell’s own components. Christian de Duve first coined the expression “autophagy” during his seminal work on the discovery of lysosomes, which led him to being awarded the Nobel Prize in Physiology or Medicine in 1974. The term was adopted to distinguish degradation of intracellular components from the uptake and degradation of extracellular substances that he called “heterophagy”. Studies until the 1990s were largely observational/morphological-based and then in 1993 Yoshinori Oshumi described a genetic screen in yeast undergoing nitrogen deprivation that led to the isolation of autophagy-defective mutants that were originally called “apg” mutant genes, but today are better known as ATG (AuTophaGy-related) genes [1]. The screen identified apg mutants that fell into 15 complementation groups implying that at least 15 genes were involved in the regulation of autophagy in yeast undergoing nutrient deprivation, but today, 41 yeast ATG genes have been described and many (though not all) have orthologues in humans. Attempts to identify the genetic basis of autophagy led to an explosion in its research, evidenced by the more than 26,000 papers listed when PubMed is queried with “autophagy”. It is not surprising then that this year (2016) Yoshinori Oshumi was awarded the Nobel Prize in Physiology or Medicine. At the time of writing there are over 5000 reviews on autophagy available via PubMed and so our aim here is not to exhaustively review the ever-expanding autophagy literature (>60 papers per week), but to celebrate Yoshinori Oshumi’s Nobel Prize by highlighting just a few aspects that are not extensively covered. In an accompanying mini- review we address the role of autophagy in early-diverging eukaryote parasites that, like yeast, lack lysosomes and so use a digestive vacuole to degrade autophagosome cargo and also discuss how parasitized host cells react to infection by subverting regulation of autophagy.