Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA 94143, USA.
Sci Signal. 2018 Apr 24;11(527):eaap8526. doi: 10.1126/scisignal.aap8526.
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 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.
米色脂肪细胞是一种富含线粒体的可诱导的产热脂肪细胞，它会在受到外部刺激（如慢性寒冷暴露）时出现。我们之前已经表明，在去除外部刺激后，米色脂肪细胞通过自噬介导的线粒体降解直接获得类似于白色脂肪的表型。我们研究了介导线粒体清除的上游途径，并报告 Parkin 介导的线粒体自噬在米色向白色脂肪细胞的转变中发挥关键作用。在基因上缺乏 的小鼠显示出线粒体降解减少，并且即使在去除外部刺激后，仍保留有产热的米色脂肪细胞。去甲肾上腺素通过 PKA 途径的信号传导抑制了 Parkin 蛋白在米色脂肪细胞中线粒体的募集。然而，线粒体质子解偶联通过解偶联蛋白 1（UCP1）对于 Parkin 的募集和米色脂肪细胞的维持是可有可无的。这些结果表明，通过线粒体自噬，外部线索通过生理机制控制产热脂肪细胞中线粒体的动态平衡。
