Exploring molecular wires that link metabolism to aging: The New Mechanisms to regulate Autophagy Negatively in mTOR-independent manner > 세미나

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세미나

Exploring molecular wires that link metabolism to aging: The New Mecha…

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  • 2016-01-04

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[BK21 Plus Seminar]

▶Subject: Exploring molecular wires that link metabolism to aging:
The New Mechanisms to regulate Autophagy Negatively in mTOR-independent manner

▶Speaker: In Hye Lee, Ph.D.
(Department of Life Science, College of Natural Science, Ewha Womans University

▶Date: 4:30 PM/Jan. 7(Thur.)/2016

▶Place: Chemisty Bldg. #401

*Abctract
Aging is considered as a process to decline organismal function, which results in collapse of body homeostasis. It increases the susceptibility to age-related diseases including neurodegenerative diseases and cardiovascular diseases. One of the attractions to study mechanism of aging is to make aging slower. One strategy to appeal is calorie restriction, which is thought to regulate life span based on scientific evidences. However the detail mechanism is not clear. Calorie restriction activates Sirt1 and induces autophagy. Autophagy is a self-eating system that degrades intracellular compartments in cells. It degrades protein aggregates, damaged organelles as a defense mechanism when cells are stressed such as starvation, hypoxia and DNA damage. We showed that Sirt1, a NAD+-dependent deacetylase interacts with autophagy-related proteins (Atgs) and regulates acetylation status of several essential Atg proteins such as Atg5,7,8 and 12 in vivo as well as in vitro. In other words, Sirt1 is a positive regulator of autophagy. Both of Sirt1 and autophagy are important in preventing aging and age-related diseases such as cancer, neurodegeneration diseases, diabetes, and so on.

To more understand the effect of calorie restriction on cells, we investigated the link between autophagy and cell cycle or cell death. Withdrawal of nutrients triggers an exit from the cell division cycle, the induction of autophagy and eventually, activation of cell death pathways. The relation, if any, between these events is not well characterized. We demonstrate that starved cells lacking the essential autophagy gene Atg7 failed to undergo G1 arrest. Independent of its E1-like activity, Atg7 can bind to the tumor suppressor p53 to regulate the transcription of the gene encoding the cell cycle inhibitor p21CDKN1A. With prolonged metabolic stress, the absence of Atg7 resulted in augmented DNA damage with increased p53-dependent apoptosis. Inhibition of the DNA damage response by deletion of the protein kinase Chk2 partially rescued Atg7-/- mice post-natal lethality. Thus, when nutrients are limited, Atg7 regulates p53-dependent cell cycle and cell death pathways.

Increasing evidence suggests excessive nutrients inhibit autophagy but the events were not well characterized. In addition, some reports show the relationship between epidemic metabolic disease, and autophagy but the mechanism is poorly understood. Here we show that that the new negative regulation of autophagy in mTOR-independent manner by postmodification of autophagic protein. It will show new relationship between autophagy and proteasome degradation. In addition this finding will contribute to understand a novel pathological mechanism of metabolic diseases. [NRF-2014R1A1A3051320, NRF-2014M3A9D8034459, NRF- 2012M3A9C5048709]

▶Inquiry: Prof. Lee, Seung-Jae(279-2351)
* This seminar will be given in Korean.
please refrain from taking photos during seminars. *

790-784 SAN 31, HYOJA-DONG, NAM-GU, POHANG, GYUNGBUK. KOREA 생체분자기능연구사업단 TEL : 054-279-2997

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