Vascular smooth muscle cells (VSMCs), known for their remarkable lifelong phenotypic plasticity, play a pivotal role in vascular pathologies through their ability to transition between different phenotypes. Our group discovered that the deficiency of the mitochondrial protein Poldip2 induces VSMC differentiation both in vivo and in vitro. Further comprehensive biochemical investigations revealed Poldip2's specific interaction with the mitochondrial ATPase caseinolytic protease chaperone subunit X (CLPX), which is the regulatory subunit for the caseinolytic protease proteolytic subunit (ClpP) that forms part of the ClpXP complex – a proteasome-like protease evolutionarily conserved from bacteria to humans. This interaction limits the protease's activity, and reduced Poldip2 levels lead to ClpXP complex activation. This finding prompted the hypothesis that ClpXP complex activity within the mitochondria may regulate the VSMC phenotype.

中文翻译：

---

线粒体蛋白酶 ClpP 是一种药物靶点，通过 SIRT1 依赖性机制控制 VSMC 表型


血管平滑肌细胞（VSMC）以其显着的终生表型可塑性而闻名，通过其在不同表型之间转换的能力在血管病理学中发挥着关键作用。我们的研究小组发现，线粒体蛋白 Poldip2 的缺乏会在体内和体外诱导 VSMC 分化。进一步全面的生化研究揭示了 Poldip2 与线粒体 ATP 酶酪蛋白分解酶伴侣 X 亚基 (CLPX) 的特异性相互作用，CLPX 是酪蛋白分解酶蛋白水解亚基 (ClpP) 的调节亚基，形成 ClpXP 复合物的一部分 - 一种进化上保守的类蛋白酶体蛋白酶从细菌到人类。这种相互作用限制了蛋白酶的活性，并且 Poldip2 水平降低导致 ClpXP 复合物激活。这一发现提出了这样的假设：线粒体内的 ClpXP 复合物活性可能调节 VSMC 表型。