Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, 305-764, Republic of Korea; Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Republic of Korea.
Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, 305-764, Republic of Korea.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):285-290. doi: 10.1016/j.bbrc.2018.06.016. Epub 2018 Jun 14.
Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). UCP1 increases the conductance of the inner mitochondrial membrane (IMM) for protons to make BAT mitochondria generate heat rather than ATP. HDAC6 is a cytosolic deacetylase for non-histone substrates to regulate various cellular processes, including mitochondrial quality control and dynamics. Here, we showed that the body temperature of HDAC6 knockout mice is slightly decreased in normal hosing condition. Interestingly, UCP1 was downregulated in BAT of HDAC6 knockout mice, which extensively linked mitochondrial thermogenesis. Mechanistically, we showed that cAMP-PKA signaling plays a key role in HDAC6-dependent UCP1 expression. Notably, the size of brown adipocytes and lipid droplets in HDAC6 knockout BAT is increased. Taken together, our findings suggested that HDAC6 contributes to mitochondrial thermogenesis in BAT by increasing UCP1 expression through cAMP-PKA signaling pathway.
线粒体解偶联蛋白 1（UCP1）负责棕色脂肪组织（BAT）的非颤抖性产热。UCP1 增加了质子通过线粒体内膜（IMM）的通透性，使 BAT 线粒体产生热量而不是 ATP。HDAC6 是一种细胞质去乙酰化酶，用于非组蛋白底物，以调节各种细胞过程，包括线粒体质量控制和动力学。在这里，我们发现 HDAC6 敲除小鼠的体温在正常饲养条件下略有下降。有趣的是，BAT 中的 UCP1 在 HDAC6 敲除小鼠中下调，这与线粒体产热广泛相关。在机制上，我们表明 cAMP-PKA 信号通路在 HDAC6 依赖性 UCP1 表达中起关键作用。值得注意的是，HDAC6 敲除 BAT 中的棕色脂肪细胞和脂滴大小增加。总之，我们的研究结果表明，HDAC6 通过 cAMP-PKA 信号通路增加 UCP1 的表达，从而促进 BAT 中的线粒体产热。
