Patrice Codogno’s comments on « From de Duve (Nobel prize 1974) to Oshumi (Nobel prize 2016): from autophagosome to lysosome a…”A 42-year autophagic flux” success story »

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Roughly thirty years after Christian de Duve coined the term “autophagy” to describe lysosomal degradation of intracellular material after sequestration in a vacuole and named the autophagosome following observation by him and others in various mammalian tissues (liver, kidney), Per Seglen coined the term the phagophore to a specialized membrane involved in the very early stage of autophagy (See Ref 1 for review). He also coined the term amphisome for a hybrid organelle between autophagosomes and endosomes (See Ref 1 for review). This provided evidence for the functional connection between endocytosis and autophagy. Today, we know that the phagophore elongates and seals to form autophagosomes by recruitment of ATG and that endocytic compartments contribute both to the early stage of autophagosome formation and to its maturation before the fusion with lysosomes. Quantum jumps in the understanding of autophagy were the discoveries of ATG in 1993 (2) and of the role of a protein conjugation system essential for the formation of autophagosome in 1998 by Ohsumi and colleagues (3). At this time ATG were known as apg (Ohsumi’ nomenclature) (3),  aut (Thumm’s nomenclature) (4) and cvt  
ohsumi

(Picture done by  Audrey Esclatine) 

(Klionsky’s nomenclature) (4) and cvt (Klionsky’s nomenclature) (5). In 2003 a unique nomenclature was decided (a wise decision!…) (6). In 1999, Levine and her co-workers revealed that the protein Beclin 1/ATG6 is encoded by a tumor suppressor gene and is a partner of Bcl-2 (7). This was the first direct evidence for the contribution of autophagy to malignancies. This article paved the way for research into the function of autophagy and of ATG in physiology and human disease. The discovery of interaction of Beclin 1 with proteins of the Bcl-2 family initiated studies of the complex crosstalk between autophagy and apoptosis.

I would like to note the sentence from a review of Seglen and Bohley in 1992 (8): “To obtain reliable information about the biochemistry of autophagy more specific assay methods would therefore be desirable.”  It is obvious that ATG-based methods have and will continue to move autophagy studies into new territories.

  1. Fengsrud M et al (2004) Structural aspect of mammalian autophagy. In Autophagy (Klionsky D.J. ed) Landes Biosciences, Georgetown, TX , pp 11-25
  2. Tsukada M & Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 333, 169-74 (1993).
  3. Mizushima, N, et al. A protein conjugation system essential for autophagy. Nature 395, 395-398 (1998)
  4. Thumm M et al. Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett. 349, 275-80 (1994).
  5. Harding TM et al. Isolation and characterization of yeast mutants in the cytoplasm to vacuole protein targeting pathway. J Cell Biol. 1995, 131:591-602 (1995).
  6. Klionsky DJ, et al.. A unified nomenclature for yeast autophagy-related genes. Dev Cell 5, 539-45 (2003).
  7. Liang, X.H., et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672-676 (1999)
  8. Seglen, P.O. & Bohley, P. Autophagy and other vacuolar protein degradation mechanisms. Experientia 48,158-72 (1992)

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