Archive for outubro 8th, 2016

Autofagia Celular: A Auto-Reciclagem da Galaxia Projetada na Célula Viva

sábado, outubro 8th, 2016

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(Artigo/tese em construcao)

Na célula vao se juntando materiais que nao funcionam mais, como organelas, proteinas, etc. Se isto continuar pode tornar a celula inoperante e leva-la a destruicao. Mas no microscopico mundo dos atomos e moleculas, surgiu um mecanismo de extraordinaria engenharia para salvar a celula. Os materiais desgastados sao reunidos, em volta deles se forma uma membrana e como um bolido este saco de materiais degradados e’ conduzido `a usina de destruicao de lixo da celula, o lisosomo. Daqui esse corpo e’ expulso para fora. Este mecanismo e’ denomainado ” autofagia” e foi descoberto pelo cientista japones Oshumi, o qual ainda descobriu 15 genes envolvidos no processo. Acontece que as vezes este mecanismo nao funciona bem e isto e’ causa de mortais doencas, como Parkinsons, diabetes, cancer, etc. Por isto Oshumi ganhou o Premio Nobel para Fisiologia e Medicina de 2016.

Tudo bem… Assim como esta escrito acima, a Ciência Academica faz seu trabalho, que e’ observar um fenomeno existente, tentar repeti-lo ou imita-lo tecnologicamente, tentar manipula-lo experimentalmente para corrigir erros, transmitir a descricao do fenomeno aos estudantes.

Porem, eu trabalho com filosofia naturalista, a qual busca se informar sobre estas informacoes que vem da Ciencia Academica ou empiricamente, tenta conectar os fenomenos num quadro para buscar uma visao de conjunto geral da Natureza. Mas nao e’ apenas conecta-los em termos de espaco, e sim, tambem conecta-los em termos de tempo, de sequencia de eventos, buscando conhecer a evolucao universal. Para isso, o filosofo naturalista, ao ler esta informacao, imediatamente se faz a pergunta: “Qual a causa”? Ou seja: como, porque e de onde a Natureza obteve forcas, recursos e informacoes, para construir este fenomeno – que no caso acima, e’ um mecanismo, ou um processo?

A Ciencia Academica descreve o que esta acontecendo no presente, pois ela apenas pode lidar com fatos existentes aqui e agora. Existe uma area derivada desta Ciencia que tenta conectar os fatos atuais com resquicios, fosseis, de teorizados fatos ou eventos ocorridos no passado, tambem buscando uma visao de conjunto, que e’ a area da teoria evolucionista.

Mas para conectar fatos entre si, no tempo, e’ preciso imaginar um mecanismo ou processo universal guiando estas conexoes. Se uma pessoa torna-se um suicida atrelando ao corpo uma bomba, imediatamente nossa mente conecta o evento da explosao com algum grupo ideologico/religioso, e esta conexao e’ o processo imaginado que explica a ocorrencia. Sendo um animal pragmatico, que busca acima de tudo sua sobrevivencia, o ser humano normalmente nao se suicida, ao menos, nao dessa maneira. Nao existe uma explicacao naturalista, materialista, racionalista, para tal processo. Somos obrigados a recorrer a abstracao e aceita-la como sendo uma forca real dirigindo tal processo.

Assim nasceram as religioes. Inventamos imaginariamente uma entidade abstrata, um mecanismo ou processo abstrato, para explicar os fatos sem conhecimento de causas que presenciamos na vida real. A teoria evolucionista nao poderia ser diferente, e o processo ou mecanismo abstrato que ela encontrou para satisfazer sua necessidade de explicacoes foi uma entidade abstrata – o Acaso Absoluto Construtor de Complexidade. Entao, como no texto da organizacao do Premio Nobel explicando o trabalho de Oshumi ( copiado abaixo para ser traduzido e rememorado), e como no texto do Professor de Biologia – PZ Myers (tambem copiado aqui abaixo), descreve-se o fato descoberto e para-se nesta descricao. Diz-se que a celula tem um mecanismo chamado autofagia… e so’. O mecanismo foi inicialmente descoberto na celula de um micro-organismo – o yeast – e depois Oshumi verificou que celulas humanas tambem apresentam o mecanismo. Se a teoria evolucionaria se ocupasse de tambem estudar as evolucoes dos mecanismos, iria investigar a diferenca entre o processo na celula do micro-organismo e o processo na celula humana, mas com certeza, as diferencias seriam imputadas a mutacoes nos genes que dirigem o processo e estas mutacoes, como acreditam, ocorrem por acaso, ou mais literalmente, por erros de transcricao na reprodução. Alguns erros -segundo esta teoria – coincidem de providenciarem melhorias ao organismo, e por isso são mantidos hereditariamente. A causa fundamental sera’ sempre o tal do acaso.

Em vista disso, o que a humanidade vai fazer na tentativa de combater as mortais doencas? Primeiro – e ja comecou a corrida entre competidores – sera descobrir drogas que inibam a proteina tal que faz tal coisa, etc. Ou seja, atuar depois do mal instalado e nao para elimina-lo de vez e sim para atenuar seus efeitos danosos. Num segundo caso e numa investigacao mais profunda, tentar-se-a’ eliminar estes genes mutados inserindo os genes originais. mas isto nao tem funcionado com estas doencas milenares mortais, elas continuam existindo.

Entao, nesta altura dos acontcimentos, entra em cena o filosofo naturalista. Ao inves de ir ao laboratorio procurar as drogas e os genes mutados, ele parou antes, ao receber a informacao da existencia do mecanismo, justo no momento que o texto diz: a celula tem um mecanismo…

Como?… a celula tem um mecanismo? Celula ‘e um amontoado de atomos que com a evolicao de junaram em moleculas, algumas se juntaram formando organelas, o DNA e o RNA, etc. Cada um destes elementos, que sao os resultados finais das diferentes combinacoes de diferentes atomos, tem sua historia evolutiva. Mas qual a historia evolutiva deste mecanismo? Como a natureza bruta e cega produziu isto, e dentro de um sistema celular?

Aqui comeca o trabalho do filosofo naturalista, e apesar de ser desprezado e, muitas vezes, motivo de ironias por parte dos investigadores cientistas que atuam com “as mãos na massa”, eu penso que a maioria dos seres humanos iriam preferir botar o guarda-po branco e correr para a mesa do laboratorio do que escrever estas perguntas no papel e começar a raciocinar buscando as respostas apenas mentalmente.  Como, porque, de onde a natureza bruta e cega obteve informacoes para criar isto?!

E entao, primeiro o filosofo tenta se concenrar na essencia, no conceito do que ele esta buscando. Neste caso o conceito e’ denominado”mecanismo”. O que e’ mecanismo? E logo vem a mente de como o homem faz um projeto no papel “criando” um mecanismo:

Assim esta desenhado um mecanismo pela inteligencia humana. Mas este desenho e’ semelhante ao desenho de um mecanismo criado pela Natureza. A celula, os organismos, contem milhares de mecanismos similares. Desde que refutei a teoria religiosa e a teoria do acaso, tive que procurar uma outra teoria para explicar como este desenho existe naturalmente. A minha teoria se inicia correndo em paralelo a teoria do acaso, porque ambas rebuscam um processo imaginario, que ‘e a evolucao. Porem o paralelismo termina ai’. Na teoria do acaso, este desenho acima teria comecado num sistema biologico, ou ainda num amontoado de atomos chamado de molecula, com uma das suas pecas, digamos, a peca numero um. Uma barra feita de atomos alinhados e’ movida como um pendulo e seu movimento de vai-e-vem por alguma forca externa, como o vento, ou a corente de fluxo sanguineo, etc. Ao assim se mover ela vai atritando com outra peca proxima – outro montoado de atomos – de maneira que vai gerando dentes nas duas pecas e assim surge uma engrenagem. na teoria do acaso o acaso estaria na existencia desta primeira barra, ela surgiu porque aomos foram empurrados para um mesmo ponto no espaco e no mesmo tempo, etc. Os acontecimentos seguintes foram nao mais por acaso e sim um mero e normal desenrolar de movimentos e seus efeitos. Ate a coisa toda culminar com o desenho acima completo. Na minha teoria, se quebrar-mos uma onda de luz natural em sete pedacos – cada qual contendo uma de suas sete vibracoes/frequencias – e solta-las livre em um mesmo ponto do espaco/tempo, elas se misturam com a substancia espacial, geram eletricidade e depois se juntam na mesma sequencia que estavam antes, e como resultado final surge um mecanismo igual ao do desenho. Mas isto nunca foi feito, e nem a natureza o fez, com uma onda de luz natural. A natureza fez este mecanismo usando sistemas que resultaram da evolucao de sistemas anteriores de maneira que regredindo no tempo, so assim entao, vamos chegar a onde de luz primordial. Entao para produzir isto na celula a natureza antes produziu-o de forma menos complexa no sistema astronimico que oriduziu a celula, e antes aindam nos atomos que produziram o sistema astronomico, e antes ainda, nas particulas… de maneira que todas estas fases da evolucao podem ser desenhadas na forma de uma formula, e nest formula se ve claramente o desenho deste mecanismo. Assim a natureza bruta e cega teria produzido esta obra de engenharia na celula vital. O problma esta na “engenharia”. Naturezas brutas e cegas nao geram engenharias. esta engenharia esta na onda de luz natural a qual veio com o Big Bang de algum lugar antes e acima do Big bang, de um lemento que produziu o Big Bang. O qual deve ser um elemento natural, porem, extra-universal, e considerando-se o seu produto, deve tratar de uma natureza mais complexa que a que vemos dentro deste Universo.

Acontece que no meu caso em particular, em que ja se conta 50 anos trabalhando este metodo, fui obtendo respostas racionais porem ainda teoricas, que explicam como a natureza criou todos os elementos envolvidos neste mecanismo, desde as organlas, as proteinas ao Dna. E acontece ainda que todas estas respostas desembocaram numa resposta universal, a qual e’ um novo processo imaginado que substitue os imaginados pelas religioes e pela Cencia Academica. Mas nao apenas os elemtnos factuais, visuas, palpaveis, chegaram na mesma resposta universal; tambem os mecanismos e processos naturais sao explicados na mesma resposta. E ela foi denominada ” Formula da Matrix/DNA”.

( Pausa: busca da definicao de “mecanismo”

Significado de Mecanismo

Dicionario portugues: Combinação de órgãos ou de peças dispostos de maneira que se obtenha um resultado determinado.Conjunto de órgãos, cuja atividade é interdependente: o mecanismo do corpo humano.[Figurado] Modo de funcionamento: o mecanismo do raciocínio ou da linguagem.

Mecanismo

Origem: Wikipédia, a enciclopédia livre.

Mecanismo em movimento

Mecanismo é um conjunto de elementos rígidos, móveis uns relativamente a outros, unidos entre si mediante diferentes tipos de junções chamadas pares cinemáticos (pernas, uniões de contato, passadores, etc.), cujo propósito é a transmissão e/ou transformação de movimentos e forças. São, portanto, as abstrações teóricas do funcionamento das máquinas, e de seu estudo se ocupa a Teoria de Mecanismos.

Baseando-se em princípios da álgebra linear e física, se criam esqueletos vetoriais, com os quais se formam sistemas de equações. A diferença de um problema de cinemática oudinâmica básico, um mecanismo não é considerado como uma massa pontual e, devido a que os elementos que conformam a um mecanismo apresentam combinações de movimentos relativos de rotação e translação, é necessário levar em conta conceitos como centro de gravidade, momento de inércia, velocidade angular, etc.

 

 

 

Autophagy wins a Nobel

http://scienceblogs.com/pharyngula/2016/10/03/autophagy-wins-a-nobel/

Posted by PZ Myers on October 3, 2016

Well, actually, Yoshinori Ohsumi has won the prize for his work on autophagy, a cellular process you may have never heard of before. The word means “self eating”, and it’s an important pathway that takes chunks of the internal content of the cell and throws them into the cell’s incinerator, the lysosome, where enzymes and reactive chemicals shred them down into their constituent amino acids and other organic compounds for reuse. What makes it interesting is that the cell doesn’t want to just indiscriminately trash internal components; there are proteins that recognize damaged organelles and malfunctioning bits and packages them up in a tidy little double membrane bound vesicle that fuses with the lysosome and destroys them.

At least, most of the time it’s selective. It was first characterized by Ohsumi in yeast, where, if you starve the cells, they start self-cannibalizing to survive. If you use mutant yeast that lack some of the degradative enzymes, they are unable to break down the materials being dumped into the lysosome, and the vacuoles just get larger and larger, making it relatively easy to screen for changes in the machinery for autophagy.

Autophagy in yeast. In starvation-induced (non-selective) autophagy,  the isolation membrane mainly non-selectively engulfs cytosolic constituents and organelles to form the autophagosome. The inner membrane-bound structure of the autophagosome (the autophagic body) is released into the vacuolar lumen following fusion of the outer membrane with the vacuolar membrane, and is disintegrated to allow degradation of the contents by resident hydrolyases. In selective autophagy, specific cargoes (protein complexes or organelles) are enwrapped by membrane vesicles that are similar to autophagosomes, and are delivered to the vacuole for degradation. Although the Cvt (cytoplasm-to-vacuole targeting) pathway mediates the biosynthetic transport of vacuolar enzymes, its membrane dynamics and mechanism are almost the same as those of selective autophagy (see the main text).

Autophagy in yeast. In starvation-induced (non-selective) autophagy, the isolation membrane mainly non-selectively engulfs cytosolic constituents and organelles to form the autophagosome. The inner membrane-bound structure of the autophagosome (the autophagic body) is released into the vacuolar lumen following fusion of the outer membrane with the vacuolar membrane, and is disintegrated to allow degradation of the contents by resident hydrolyases. In selective autophagy, specific cargoes (protein complexes or organelles) are enwrapped by membrane vesicles that are similar to autophagosomes, and are delivered to the vacuole for degradation. Although the Cvt (cytoplasm-to-vacuole targeting) pathway mediates the biosynthetic transport of vacuolar enzymes, its membrane dynamics and mechanism are almost the same as those of selective autophagy (see the main text)

Taking out the trash is a vital procedure for cells, as well as for maintenance of your household, and there are cases where autophagy is implicated in human diseases. For instance, mitochondria are intensely active metabolically, and experience a lot of wear and tear. Your cells take old, busted mitochondria, tag them with proteins, and recycle them with a specific subset of autophagy called mitophagy, or mitochondria-eating. Some forms of Parkinson’s disease seem to be caused by defects in the mitophagy machinery, causing defective mitochondria to accumulate in the cell and impairing normal function.

Autophagy also seems to have some complex roles in cancer. It can be a good thing, in that early on if defective proteins and organelles accumulate, they can be sensed and destroyed, so autophagy in that case is a defense against cancer. However, cancer can also subvert that machinery and route the cell’s defenses right into the trash.

But also, autophagy seems to be involved in every step in cancer metastasis. This shouldn’t be a surprise, since autophagy is used to regulate the activity of the cell in all kinds of behaviors.

Schematic illustrating roles of autophagy in the metastatic cascade. Autophagy increases as tumor cells progress to invasiveness and this in turn is linked to increased cell motility, EMT, a stem cell phenotype, secretion of pro-migratory factors, release of MMPs, drug resistance and escape from immune surveillance at the primary site in some tumors. Many aspects of these autophagy-dependent changes during acquisition of invasiveness also likely contribute to the ability of disseminating tumor cells to intravasate, survive and migrate in the circulation before extravasating at secondary site. At the secondary site, autophagy is required to maintain tumor cells in a dormant state, possibly through its ability to promote quiescence and a stem cell phenotype, that in turn is linked to tumor cell survival and drug resistance. Emerging functions for autophagy in metastasis include a role in establishing the pre-metastatic niche as well as promoting tumor cell survival, escape from immune surveillance and other aspects required to ultimately grow out an overt metastasis.

Schematic illustrating roles of autophagy in the metastatic cascade. Autophagy increases as tumor cells progress to invasiveness and this in turn is linked to increased cell motility, EMT, a stem cell phenotype, secretion of pro-migratory factors, release of MMPs, drug resistance and escape from immune surveillance at the primary site in some tumors. Many aspects of these autophagy-dependent changes during acquisition of invasiveness also likely contribute to the ability of disseminating tumor cells to intravasate, survive and migrate in the circulation before extravasating at secondary site. At the secondary site, autophagy is required to maintain tumor cells in a dormant state, possibly through its ability to promote quiescence and a stem cell phenotype, that in turn is linked to tumor cell survival and drug resistance. Emerging functions for autophagy in metastasis include a role in establishing the pre-metastatic niche as well as promoting tumor cell survival, escape from immune surveillance and other aspects required to ultimately grow out an overt metastasis.

It may also affect Crohn’s disease and other inflammatory syndromes. There are mutated proteins associated with Crohn’s that are part of the autophagy pathway; macrophages carrying these mutations deliver bigger doses of inflammatory cytokines when stimulated. Selective autophagy plays a role in regulating the balance of exports from the cell.

Those are the mild diseases caused by defects in this pathway. Look up Vici syndrome, a heritable disorder that causes devastating problems for those afflicted. It’s caused by mutations in the EPG5 gene, which is an important regulator of autophagy.

It’s not just about human diseases, though. Autophagy is universal in eukaryotes: yeast have it, plants have it, animals have it. Genes in the pathway are studied in yeast and nematodes and flies and mice, so this is a common mechanism of regulating the internal traffic of the cell.

Procurar estas referencias:

Jiang P, Mizushima N (2014) Autophagy and human diseases. Cell Res 24(1):69-79.

Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y (2009) Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol 10(7):458-67.

Mowers EE, Sharifi MN, Macleod KF (2016) Autophagy in cancer metastasis. Oncogene doi: 10.1038/onc.2016.333.

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Nobel Prize Org.

The Nobel Prize in Physiology or Medicine 2016
Yoshinori Ohsumi

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2016/press.html

Press Release

2016-10-03

The Nobel Assembly at Karolinska Institutet has today decided to award

the 2016 Nobel Prize in Physiology or Medicine

to

Yoshinori Ohsumi

for his discoveries of mechanisms for autophagy

Summary

This year’s Nobel Laureate discovered and elucidated mechanisms underlying autophagy, a fundamental process for degrading and recycling cellular components.

The word autophagy originates from the Greek words auto-, meaning “self”, and phagein, meaning “to eat”. Thus,autophagy denotes “self eating”. This concept emerged during the 1960’s, when researchers first observed that the cell could destroy its own contents by enclosing it in membranes, forming sack-like vesicles that were transported to a recycling compartment, called the lysosome, for degradation. Difficulties in studying the phenomenon meant that little was known until, in a series of brilliant experiments in the early 1990’s, Yoshinori Ohsumi used baker’s yeast to identify genes essential for autophagy. He then went on to elucidate the underlying mechanisms for autophagy in yeast and showed that similar sophisticated machinery is used in our cells.

Ohsumi’s discoveries led to a new paradigm in our understanding of how the cell recycles its content. His discoveries opened the path to understanding the fundamental importance of autophagy in many physiological processes, such as in the adaptation to starvation or response to infection. Mutations in autophagy genes can cause disease, and the autophagic process is involved in several conditions including cancer and neurological disease.

Degradation – a central function in all living cells

In the mid 1950’s scientists observed a new specialized cellular compartment, called an organelle, containing enzymes that digest proteins, carbohydrates and lipids. This specialized compartment is referred to as a “lysosome” and functions as a workstation for degradation of cellular constituents. The Belgian scientist Christian de Duve was awarded the Nobel Prize in Physiology or Medicine in 1974 for the discovery of the lysosome. New observations during the 1960’s showed that large amounts of cellular content, and even whole organelles, could sometimes be found inside lysosomes. The cell therefore appeared to have a strategy for delivering large cargo to the lysosome. Further biochemical and microscopic analysis revealed a new type of vesicle transporting cellular cargo to the lysosome for degradation (Figure 1). Christian de Duve, the scientist behind the discovery of the lysosome, coined the term autophagy, “self-eating”, to describe this process. The new vesicles were named autophagosomes.

Autophagosome.

Figure 1: Our cells have different specialized compartments. Lysosomes constitute one such compartment and contain enzymes for digestion of cellular contents. A new type of vesicle called autophagosome was observed within the cell. As the autophagosome forms, it engulfs cellular contents, such as damaged proteins and organelles. Finally, it fuses with the lysosome, where the contents are degraded into smaller constituents. This process provides the cell with nutrients and building blocks for renewal.

During the 1970’s and 1980’s researchers focused on elucidating another system used to degrade proteins, namely the “proteasome”. Within this research field Aaron Ciechanover, Avram Hershko and Irwin Rose were awarded the 2004 Nobel Prize in Chemistry for “the discovery of ubiquitin-mediated protein degradation”. The proteasome efficiently degrades proteins one-by-one, but this mechanism did not explain how the cell got rid of larger protein complexes and worn-out organelles. Could the process of autophagy be the answer and, if so, what were the mechanisms?

A groundbreaking experiment

Yoshinori Ohsumi had been active in various research areas, but upon starting his own lab in 1988, he focused his efforts on protein degradation in the vacuole, an organelle that corresponds to the lysosome in human cells. Yeast cells are relatively easy to study and consequently they are often used as a model for human cells. They are particularly useful for the identification of genes that are important in complex cellular pathways. But Ohsumi faced a major challenge; yeast cells are small and their inner structures are not easily distinguished under the microscope and thus he was uncertain whether autophagy even existed in this organism. Ohsumi reasoned that if he could disrupt the degradation process in the vacuole while the process of autophagy was active, then autophagosomes should accumulate within the vacuole and become visible under the microscope. He therefore cultured mutated yeast lacking vacuolar degradation enzymes and simultaneously stimulated autophagy by starving the cells. The results were striking! Within hours, the vacuoles were filled with small vesicles that had not been degraded (Figure 2). The vesicles were autophagosomes and Ohsumi’s experiment proved that authophagy exists in yeast cells. But even more importantly, he now had a method to identify and characterize key genes involved this process. This was a major break-through and Ohsumi published the results in 1992.

Yeast.

Figure 2: In yeast (left panel) a large compartment called the vacuole corresponds to the lysosome in mammalian cells. Ohsumi generated yeast lacking vacuolar degradation enzymes. When these yeast cells were starved, autophagosomes rapidly accumulated in the vacuole (middle panel). His experiment demonstrated that autophagy exists in yeast. As a next step, Ohsumi studied thousands of yeast mutants (right panel) and identified 15 genes that are essential for autophagy.

Autophagy genes are discovered

Ohsumi now took advantage of his engineered yeast strains in which autophagosomes accumulated during starvation. This accumulation should not occur if genes important for autophagy were inactivated. Ohsumi exposed the yeast cells to a chemical that randomly introduced mutations in many genes, and then he induced autophagy. His strategy worked! Within a year of his discovery of autophagy in yeast, Ohsumi had identified the first genes essential for autophagy. In his subsequent series of elegant studies, the proteins encoded by these genes were functionally characterized. The results showed that autophagy is controlled by a cascade of proteins and protein complexes, each regulating a distinct stage of autophagosome initiation and formation (Figure 3).

Stages of autophagosome formation

Figure 3: Ohsumi studied the function of the proteins encoded by key autophagy genes. He delineated how stress signals initiate autophagy and the mechanism by which proteins and protein complexes promote distinct stages of autophagosome formation.

Autophagy – an essential mechanism in our cells

After the identification of the machinery for autophagy in yeast, a key question remained. Was there a corresponding mechanism to control this process in other organisms? Soon it became clear that virtually identical mechanisms operate in our own cells. The research tools required to investigate the importance of autophagy in humans were now available.

Thanks to Ohsumi and others following in his footsteps, we now know that autophagy controls important physiological functions where cellular components need to be degraded and recycled. Autophagy can rapidly provide fuel for energy and building blocks for renewal of cellular components, and is therefore essential for the cellular response to starvation and other types of stress. After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging.

Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. Intense research is now ongoing to develop drugs that can target autophagy in various diseases.

Autophagy has been known for over 50 years but its fundamental importance in physiology and medicine was only recognized after Yoshinori Ohsumi’s paradigm-shifting research in the 1990’s. For his discoveries, he is awarded this year’s Nobel Prize in physiology or medicine.

Key publications

Takeshige, K., Baba, M., Tsuboi, S., Noda, T. and Ohsumi, Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. Journal of Cell Biology 119, 301-311

Tsukada, M. and Ohsumi, Y. (1993). Isolation and characterization of autophagy-defective mutants of Saccharomyces cervisiae. FEBS Letters 333, 169-174

Mizushima, N., Noda, T., Yoshimori, T., Tanaka, Y., Ishii, T., George, M.D., Klionsky, D.J., Ohsumi, M. and Ohsumi, Y. (1998). A protein conjugation system essential for autophagy. Nature 395, 395-398

Ichimura, Y., Kirisako T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., Noda, T. and Ohsumi, Y. (2000). A ubiquitin-like system mediates protein lipidation. Nature, 408, 488-492

 

Yoshinori Ohsumi was born 1945 in Fukuoka, Japan. He received a Ph.D. from University of Tokyo in 1974. After spending three years at Rockefeller University, New York, USA, he returned to the University of Tokyo where he established his research group in 1988. He is since 2009 a professor at the Tokyo Institute of Technology.

 

The Nobel Assembly, consisting of 50 professors at Karolinska Institutet, awards the Nobel Prize in Physiology or Medicine. Its Nobel Committee evaluates the nominations. Since 1901 the Nobel Prize has been awarded to scientists who have made the most important discoveries for the benefit of mankind.