BROWSE

Related Scientist

Researcher

채세현
식물 노화·수명 연구단
more info

Attenuating MKRN1 E3 ligase-mediated AMPKα suppression increases tolerance against metabolic stresses in mice

Cited 0 time in webofscience Cited 0 time in scopus
12 Viewed 1 Downloaded
Title
Attenuating MKRN1 E3 ligase-mediated AMPKα suppression increases tolerance against metabolic stresses in mice
Author(s)
Hyunji Han; Sehyun Chae; Daehee Hwang; Jaewhan Song
Publication Date
2018-11
Journal
Cell stress, v.2, no.11, pp.325 - 328
Publisher
Shared Science Publishers
Abstract
The 5′ adenosine monophosphate-activated protein kinase (AMPK) is an essential energy sensor in the cell, which, at low energy levels, instigates the cellular energy-generating systems along with suppression of the anabolic signaling pathways. The activation of AMPK through phosphorylation is a well-known process; however, activation alone is not sufficient, and knowledge about the other regulatory networks of post-translational modifications connecting the activities of AMPK to systemic metabolic syndromes is important, which is still lacking. The recent studies on Makorin Ring Finger Protein 1 (MKRN1) mediating the ubiquitination and proteasome-dependent degradation of AMPKa implicate that the post-translational modification of AMPK, regulating its protein homeostasis, could impose significant systemic metabolic effects (Lee et al. Nat Commun 9:3404). In this study, MKRN1 was identified as a novel E3 ligase for both AMPKα1 and α2. Mouse embryonic fibroblasts, genetically deleted for Mkrmn1, and Ampkα1 and α2, became stabilized with the suppression of lipogenesis pathways and an increase in nutrient consumption and mitochondria regeneration. Of note, the Mkrn1 knockout mice fed normal chow displayed no obvious phenotypic defects or abnormality, whereas the Mkrn1-null mice exhibited strong tolerance to metabolic stresses induced by high-fat diet (HFD). Thus, these mice, when compared with the HFD-induced wild type, were resistant to obesity, diabetes, and non-alcoholic fatty liver disease. Interestingly, in whole-body Mkrn1 knockout mouse, only the liver and white and brown adipose tissues displayed anincrease in the active phosphorylated AMPK levels, but no other organs, such as the hypothalamus, skeletal muscles, or pancreas, displayed such increases. Specific ablation of MKRN1 in the mouse liver using adenovirus prevented HFD-induced lipid accumulation in the liver and blood, implicating MKRN1 as a possible therapeutic target for metabolic syndromes, such as obesity, type II diabetes, and fat liver diseases. This study would provide a crucial perspective on the importance of post-translational regulation of AMPK in metabolic pathways and will help researchers develop novel therapeutic strategies that target not only AMPK but also its regulators.© 2018 Han et al.
URI
https://pr.ibs.re.kr/handle/8788114/5405
ISSN
2523-0204
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > Journal Papers (저널논문)
Files in This Item:
Cell Stress_2(11) 325-328.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse