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Effect of mitochondrial stress on systemic metabolism

Authors
 Myung-Shik Lee 
Citation
 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, Vol.1350 : 61-65, 2015 
Journal Title
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
ISSN
 0077-8923 
Issue Date
2015
MeSH
Animals ; Autophagy/drug effects ; Biomarkers/metabolism ; Energy Metabolism*/drug effects ; Fibroblast Growth Factors/metabolism ; Humans ; Hypoglycemic Agents/adverse effects ; Metformin/adverse effects ; Mitochondria/drug effects ; Mitochondria/enzymology ; Mitochondria/metabolism* ; Mitochondrial Diseases/chemically induced ; Mitochondrial Diseases/etiology* ; Mitochondrial Diseases/metabolism ; Models, Biological* ; Stress, Physiological*/drug effects
Keywords
FGF21 ; longevity ; metabolism ; mitochondrial stress ; mitokine
Abstract
In our studies investigating the role of autophagy in systemic metabolism, we found that mitochondrial dysfunction due to autophagy deficiency in insulin target tissues, such as skeletal muscle or liver, leads to the induction of fibroblast growth factor (FGF)21 as a mitokine and protection against obesity and insulin resistance. In the following studies, we observed that metformin, one of the most widely used antidiabetic medications, induces mitochondrial stress and induces FGF21 through a PERK-eIF2α-ATF4 pathway, which may contribute to the antidiabetic effect of metformin. Amino acid deprivation also induced ATF4 and FGF21, while the role of mitochondrial dysfunction in this condition is not yet clear. These results suggest the possibility that mitochondrial stress inducing an integrated stress response can induce a mitokine response and affect systemic metabolism in a non-cell-autonomous manner, in addition to the well-recognized cell-autonomous role of mitochondrial function in metabolism.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/nyas.12822/abstract
DOI
10.1111/nyas.12822
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Lee, Myung Shik(이명식) ORCID logo https://orcid.org/0000-0003-3292-1720
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/156914
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