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

Abstract

Christian de Duve first coined the expression “autophagy” during his seminal work on the discovery of lysosomes, which led to him 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 until in 1993 Yoshinori Oshumi described a genetic screen in yeast undergoing nitrogen deprivation that led to the isolation of autophagy-defective mutants now better known as ATG (AuTophaGy-related) genes. The screen identified 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 and it's not surprising that in 2016 Yoshinori Oshumi was awarded the Nobel Prize in Physiology or Medicine. 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 normally 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.

The parasitic worm product ES-62 normalises the gut microbiota/bone marrow axis in inflammatory arthritis

“…Consistent with this, ES-62 can rewire BM progenitors and stromal cells from CIA mice to an anti-inflammatory, regulatory or tissue repair phenotype 2,39,43,46,76,77 by subverting TLR4 signalling to prevent the up-regulation of the key TLR signal transducer, MyD88 observed during chronic inflammation 78,79 . Interestingly, therefore, given the increased incidence and severity of CIA in ES-62-ABX mice, we show that ES-62 dampening of aberrant MyD88 expression is abolished by ABX treatment and indeed, that MyD88 is expressed at equivalent levels in BM from PBS-CIA, PBS-ABX and ES-62-ABX mice (Fig.…”

Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

“…Lysosomes contain hydrolases that participate in the digestion of substrates that come either from outside or from inside the cell. Autophagy has been initially defined by Christian De Duve as a self-eating process, i.e., a process allowing cell to digest and recycle unnecessary or harmful intracellular components, in opposition with heterophagy, a process allowing cells to degrade extracellular material [76]. Although once considered an exclusive degradative process, it is now acknowledged that autophagy has also important signaling and metabolic function, being able to finely tune the degradation of specific substrates according to cellular needs.…”

Characterizing Adversity of Lysosomal Accumulation in Nonclinical Toxicity Studies: Results from the 5th ESTP International Expert Workshop

“…They facilitate degradation of extracellular material as well as intracellular components and contribute to many other key cellular processes such as plasma membrane repair, cholesterol homeostasis, antigen presentation, and cell death (Xu and Ren 2015). The fundamental pathophysiological relevance of lysosomal function is highlighted by the fact that the Nobel Prize for Physiology or Medicine has been granted twice for lysosomal research to Christian de Duve for their initial discovery as organelles (Bainton 1981) and, more recently, to Yoshinori Oshumi for elucidation of the process of autophagy (Harnett et al 2017).…”