論文

査読有り
2015年6月

Translocase of inner mitochondrial membrane 44 alters the mitochondrial fusion and fission dynamics and protects from type 2 diabetes

METABOLISM-CLINICAL AND EXPERIMENTAL
  • Yu Wang
  • ,
  • Akihiro Katayama
  • ,
  • Takahiro Terami
  • ,
  • Xiaoying Han
  • ,
  • Tomokazu Nunoue
  • ,
  • Dongxiao Zhang
  • ,
  • Sanae Teshigawara
  • ,
  • Jun Eguchi
  • ,
  • Atsuko Nakatsuka
  • ,
  • Kazutoshi Murakami
  • ,
  • Daisuke Ogawa
  • ,
  • Yasuhide Furuta
  • ,
  • Hirofumi Makino
  • ,
  • Jun Wada

64
6
開始ページ
677
終了ページ
688
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.metabol.2015.02.004
出版者・発行元
W B SAUNDERS CO-ELSEVIER INC

Objective. In obesity and type 2 diabetes, the impairment of mitochondrial function in white adipose tissue (WAT) is linked to a reduction in whole body insulin sensitivity. Timm44 is upregulated in the kidneys of streptozotocin-induced diabetic mice. In the inner mitochondrial membrane, Timm44 anchors mitochondrial heat-shock protein 70 (mtHsp70) to the translocase of inner mitochondrial membrane 23 (TIM23) complex and facilitates the import of mitochondria-targeted preproteins into the mitochondrial matrix dependent on the inner membrane potential and ATP hydrolysis on ATPase domain of mtHsp70.
Methods. We generated the aP2-promoter driven Timm44 transgenic (Tg) mouse model and investigated whether Timm44 Tg mice fed high-fat/high-sucrose (HFHS) chow are protected from type 2 diabetes and obesity.
Results. The body weight of aP2-promoter driven Timm44 Tg mice was lower than that of wild type mice, and insulin sensitivity was greater in Timm44 Tg mice than in wild type mice. Although WAT weight was not altered in Timm44 Tg mice fed HFHS chow, adipocyte size was reduced, and mitochondrial fusion associated with decreased expression of fission genes, such as Dnm11 and Fis1, was observed. In addition, when fed standard (STD) chow, the expressions of the fusion genes Opal, Mfn1 and Mfn2, and Mfn1 were significantly increased in Timm44 Tg mice compared to wild type mice, and fused mitochondria were also observed in Timm44 Tg mice fed STD chow.
Conclusions. The Timm44 gene may be a new target for the treatment of type 2 diabetes. (C) 2015 Elsevier Inc. All rights reserved.

Web of Science ® 被引用回数 : 16

リンク情報
DOI
https://doi.org/10.1016/j.metabol.2015.02.004
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000353527400004&DestApp=WOS_CPL
URL
http://orcid.org/0000-0003-1468-5170
ID情報
  • DOI : 10.1016/j.metabol.2015.02.004
  • ISSN : 0026-0495
  • eISSN : 1532-8600
  • ORCIDのPut Code : 17921301
  • Web of Science ID : WOS:000353527400004

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