Capera Jesusa, Pérez-Verdaguer Mireia, Navarro-Pérez María, Felipe Antonio
Molecular Physiology Laboratory, Departament de Bioquímica i Biomedicina Molecular, Institut de Biomedicina (IBUB), Universitat de Barcelona, 08028 Barcelona, Spain.
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.
Cancers (Basel). 2021 Sep 4;13(17):4457. doi: 10.3390/cancers13174457.
The voltage-gated potassium channel Kv1.3 is a potential therapeutic target for obesity and diabetes. The genetic ablation and pharmacological inhibition of Kv1.3 lead to a lean phenotype in rodents. The mechanism of regulation of body weight and energy homeostasis involves Kv1.3 expression in different organs, including white and brown adipose tissues. Here, we show that Kv1.3 promotes the proliferation of preadipocytes through the control of mitochondrial dynamics. Kv1.3 is expressed in mitochondria exhibiting high affinity for the perinuclear population. The mitochondrial network is highly dynamic during the cell cycle, showing continuous fusion-fission events. The formation of a hyperfused mitochondrial network at the G1/S phase of the cell cycle is dependent on Kv1.3 expression. Our results demonstrate that Kv1.3 promotes preadipocyte proliferation and differentiation by controlling mitochondrial membrane potential and mitochondrial dynamics at the G1 phase of the cell cycle.
电压门控钾通道Kv1.3是肥胖和糖尿病的潜在治疗靶点。对Kv1.3进行基因敲除和药物抑制可使啮齿动物呈现瘦型表型。体重调节和能量稳态的机制涉及Kv1.3在不同器官中的表达，包括白色和棕色脂肪组织。在此，我们表明Kv1.3通过控制线粒体动力学促进前脂肪细胞增殖。Kv1.3在线粒体中表达，对核周群体具有高亲和力。线粒体网络在细胞周期中高度动态，呈现持续的融合-裂变事件。细胞周期G1/S期超融合线粒体网络的形成依赖于Kv1.3的表达。我们的结果表明，Kv1.3通过在细胞周期G1期控制线粒体膜电位和线粒体动力学来促进前脂肪细胞的增殖和分化。
