ミトコンドリアのROSはUCP1の熱生成エネルギー消費と硫化を調節する

Edward T Chouchani^1,2, Lawrence Kazak^1,2, Mark P Jedrychowski²

¹Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.

Nature

|March 31, 2016

まとめ

ミトコンドリアの反応性酸素種 (ROS) は茶色脂肪組織発熱に不可欠です. この発見は肥満や糖尿病のような代謝障害に対する新しい治療目標を提供します

科学分野:

細胞生物学
代謝に関する研究
脂肪組織生物学

背景:

茶色とベージュの脂肪組織は,解離タンパク質1 (UCP1) に依存した熱的呼吸によって熱としてエネルギーを放散する.
脂肪細胞におけるUCP1依存の熱生成は,肥満と糖尿病との闘いに役立つ可能性がある.
UCP1依存呼吸を制御する要因を理解することは,代謝疾患の治療にとって不可欠である.

研究の目的:

ブラウン脂肪組織 (BAT) の熱生成におけるミトコンドリアの活性酸素種 (ROS) の役割を調査する.
ROSがUCP1に依存した呼吸と全身のエネルギー消費に不可欠であるかどうかを判断する.
ROS が UCP1 の活動を調節する分子メカニズムを解明する.

主な方法:

青い脂肪組織の熱生成を刺激する
ミトコンドリアのROSレベルの薬理学的操作
UCP1依存の呼吸と全身のエネルギー消費の測定
システイン・チオール・レドックス状態とタンパク質・スルフェニル化の分析,特にUCP1 Cys253を標的とする.

主要な成果:

BATにおける急激に活性化された熱生成は,ミトコンドリアのROS濃度の上昇によって特徴付けられます.
ミトコンドリアのROSの薬理学的枯渇は,体内の発熱を阻害し,UCP1に依存するエネルギー消費を減少させます.
熱生成のROSは,BATにおけるシステインチオールの酸化還元状態を変化させ,呼吸を促進します.
UCP1 Cys253は発熱過程でスルフェニル化され,その変異はUCP1の活性とアドレナージック活性に影響する.

結論:

茶色脂肪組織におけるミトコンドリアのROS誘導は,UCP1依存の熱生成をサポートする重要なメカニズムである.
ROS媒介によるUCP1の調節は全身のエネルギー消費に不可欠である.
これらの発見は肥満や糖尿病などの代謝障害に対する治療的介入の新たな経路を示しています

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