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Transaldolase inhibition impairs mitochondrial respiration and induces a starvation-like longevity response in Caenorhabditis elegans
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نویسنده
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bennett c.f. ,kwon j.j. ,chen c. ,russell j. ,acosta k. ,burnaevskiy n. ,crane m.m. ,bitto a. ,vander wende h. ,simko m. ,pineda v. ,rossner r. ,wasko b.m. ,choi h. ,chen s. ,park s. ,jafari g. ,sands b. ,perez olsen c. ,mendenhall a.r. ,morgan p.g. ,kaeberlein m.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 3
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چکیده
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Mitochondrial dysfunction can increase oxidative stress and extend lifespan in caenorhabditis elegans. homeostatic mechanisms exist to cope with disruptions to mitochondrial function that promote cellular health and organismal longevity. previously,we determined that decreased expression of the cytosolic pentose phosphate pathway (ppp) enzyme transaldolase activates the mitochondrial unfolded protein response (uprmt) and extends lifespan. here we report that transaldolase (tald-1) deficiency impairs mitochondrial function in vivo,as evidenced by altered mitochondrial morphology,decreased respiration,and increased cellular h2o2levels. lifespan extension from knockdown of tald-1 is associated with an oxidative stress response involving p38 and c-jun n-terminal kinase (jnk) mapks and a starvation-like response regulated by the transcription factor eb (tfeb) homolog hlh-30. the latter response promotes autophagy and increases expression of the flavin-containing monooxygenase 2 (fmo-2). we conclude that cytosolic redox established through the ppp is a key regulator of mitochondrial function and defines a new mechanism for mitochondrial regulation of longevity. © 2017 bennett et al.
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آدرس
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department of pathology,university of washington,seattle,wa,united states,molecular and cellular biology program,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa,united states,molecular medicine and mechanisms of disease program,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, division of basic sciences,fred hutchinson cancer research center,seattle,wa, United States, division of basic sciences,fred hutchinson cancer research center,seattle,wa, United States, department of pathology,university of washington,seattle,wa, United States, center for integrated brain research,seattle children’s research institute,seattle,wa,united states,department of anesthesiology,university of washington school of medicine,seattle,wa, United States, department of pathology,university of washington,seattle,wa,united states,molecular and cellular biology program,university of washington,seattle,wa,united states,molecular medicine and mechanisms of disease program,university of washington,seattle,wa, United States
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Authors
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