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2016 Nobel Prize Laureate in Medicine: Yoshinori OHSUMI

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发表于 10-3-2016 17:36:12 | 只看该作者 回帖奖励 |倒序浏览 |阅读模式
(1) Yoshinori OHSUMI  大隅 良典
(a) Another way to transliterate the name is Yoshinori ŌSUMI (both Ō and OH signal a long vowel of "O").
(b) Japanese-English dictionary:
* nori 典 【のり】 (n): "rule; law"
* sumi 隅 (P); 角 【すみ】 (n): "corner; nook; recess"

(2) Press Release. The Nobel Prize in Physiology and Medicine 2016.
https://www.nobelprize.org/nobel ... tes/2016/press.html

Figure 1 shows that in a human, an autophagosome (including things to be degraded) fuses with a lysosome (containing enzymes to degrade). But a yeast has a vacuole (equivalent to lysosome, containing enzymes) INTO which an autophagosome will enter. Figure 2 (left panel).

But, the 2004 Nobel prize winners in medicine (on proteosome which degrades individual proteins) "did not explain how the cell got rid of larger protein complexes and worn-out organelles." Here is the contributionof profgessor Ohsumi.

In 1963, Christian de Duve
https://en.wikipedia.org/wiki/Christian_de_Duve
coined the term "autophagy" to describe the recycling of "larger protein complexes and worn-out organelles," which turns out to be conserved from yeast to human. Professor Ohsumi did the work to tease out the mechanism, sequences, and genes (hence proteins) involved in autophagy, in yeast.

(3) In his own words. This is the only recent review of his with illustrations.

Kuninori Suzuki and Yoshinori Ohsumi, Current Knowledge of the Pre-Autophagosomal Structure (PAS). FEBS Letters, 584: 1280–1286 (2010) (Review).
http://onlinelibrary.wiley.com/d ... et.2010.02.001/full

(a) Figure 1 tells you that in yeast, a phagosome is created only upon starvation (a yeast in nutrients-rich condition also needs to do autophagy, albeit in a smaller scale and thus with a smaller "cvt vesicle" (see (b) below) for the acronym) which in a sense is similar in terms of mechanism and genes involved). The reasons:

"When yeast cells are challenged by nitrogen-depleted conditions, sporulation and meiotic cell division are induced. It is clear that this remarkable cell differentiation and remodeling process in the absence of nitrogen supply must require bulk protein degradation of a cell's own proteins."
Yoshinori Ohsumi, Historical Landmarks of Autophagy Research. Cell Res 24: 9–23 (2014).
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3879711/

In other words, in nitrogen-depleted conditions (ie, starvation; proteins contain nitrogen, but not sugar or oil), a yeast survives by turning into haploid spores.

(b) Paragraph 1 in section 2
(i) first explains what cvt stands for: "cvt (cytoplasm-to-vacuole targeting)."
(ii) "Subsequent analysis revealed that the APG, AUT, and CVT genes largely overlap. Recently, the apg, aut, cvt, and other genes essential for selective organelle degradation have been unified as ATG (autophagy-related) to avoid confusion."

So you just have to learn ATG genes, and the proteins they produce (their functions, too).
(c) Read the paragraph before Figure 2, Figure 2 itself (including its caption).
(d) Read the the paragraphs below Figure 2.

The third paragraph mentions E1, E2, and E3. For these, go to ubiquitin
https://en.wikipedia.org/wiki/Ubiquitin
(read paragraph 1 and the first sentence of paragraph 2, of Introduction; the illustration in section 5 Ubiquitination)

Consequently, autophagy involves unique proteins (from some ATG genes) but also shares some proteins with those discovered by 2004 Nobel laureates.


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