Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism.
Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism.
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DOI：
10.1126/scisignal.aap8526
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发表时间：
2018-04-24
影响因子：
7.3
通讯作者：
Kajimura S
中科院分区：
文献类型：
--
作者：
Lu X;Altshuler-Keylin S;Wang Q;Chen Y;Henrique Sponton C;Ikeda K;Maretich P;Yoneshiro T;Kajimura S
米色脂肪细胞是一种可诱导形式的富含脂肪酸的产热脂肪细胞，其响应于外部刺激（如慢性冷暴露）而出现。我们以前已经证明，在外部刺激撤回后，米色脂肪细胞直接获得一个白色脂肪样表型通过自噬介导的线粒体降解。我们研究了介导线粒体清除的上游途径，并报道了帕金森介导的线粒体自噬在米色至白色脂肪细胞转变中起关键作用。Park2基因缺陷的小鼠表现出线粒体降解减少，即使在外部刺激撤销后仍保留产热米色脂肪细胞。通过PKA途径的去甲肾上腺素信号传导抑制了米色脂肪细胞中帕金蛋白向线粒体的募集。然而，线粒体质子解偶联解偶联蛋白1（UCP1）是帕金招聘和米色脂肪细胞的维护。这些结果提示了一种生理机制，即外部线索通过线粒体自噬控制产热脂肪细胞的线粒体稳态。
Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat-like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition. Mice genetically deficient in Park2 showed reduced mitochondrial degradation and retained thermogenic beige adipocytes even after the withdrawal of external stimuli. Norepinephrine signaling through the PKA pathway inhibited the recruitment of Parkin protein to mitochondria in beige adipocytes. However, mitochondrial proton uncoupling by uncoupling protein 1 (UCP1) was dispensable for Parkin recruitment and beige adipocyte maintenance. These results suggest a physiological mechanism by which external cues control mitochondrial homeostasis in thermogenic fat cells through mitophagy.
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影响因子：
29
作者：
Kajimura S;Spiegelman BM;Seale P
通讯作者：
Seale P
影响因子：
29
作者：
Altshuler-Keylin S;Shinoda K;Hasegawa Y;Ikeda K;Hong H;Kang Q;Yang Y;Perera RM;Debnath J;Kajimura S
通讯作者：
Kajimura S
影响因子：
64.5
作者：
Moscat, Jorge;Karin, Michael;Diaz-Meco, Maria T.
通讯作者：
Diaz-Meco, Maria T.
影响因子：
7.3
作者：
Altshuler-Keylin S;Kajimura S
通讯作者：
Kajimura S
影响因子：
5.2
作者：
Collins S
通讯作者：
Collins S