Dudek Jan
Department of Cellular Biochemistry, University Medical Center Göttingen, Göttingen, Germany.
Front Cell Dev Biol. 2017 Sep 29;5:90. doi: 10.3389/fcell.2017.00090. eCollection 2017.
The phospholipid cardiolipin (CL) is an essential constituent of mitochondrial membranes and plays a role in many mitochondrial processes, including respiration and energy conversion. Pathological changes in CL amount or species composition can have deleterious consequences for mitochondrial function and trigger the production of reactive oxygen species. Signaling networks monitor mitochondrial function and trigger an adequate cellular response. Here, we summarize the role of CL in cellular signaling pathways and focus on tissues with high-energy demand, like the heart. CL itself was recently identified as a precursor for the formation of lipid mediators. We highlight the concept of CL as a signaling platform. CL is exposed to the outer mitochondrial membrane upon mitochondrial stress and CL domains serve as a binding site in many cellular signaling events. During mitophagy, CL interacts with essential players of mitophagy like Beclin 1 and recruits the autophagic machinery by its interaction with LC3. Apoptotic signaling pathways require CL as a binding platform to recruit apoptotic factors such as tBid, Bax, caspase-8. CL required for the activation of the inflammasome and plays a role in inflammatory signaling. As changes in CL species composition has been observed in many diseases, the signaling pathways described here may play a general role in pathology.
磷脂心磷脂（CL）是线粒体膜的重要组成部分，在许多线粒体过程中发挥作用，包括呼吸作用和能量转换。CL含量或种类组成的病理变化可能对线粒体功能产生有害影响，并引发活性氧的产生。信号网络监测线粒体功能并触发适当的细胞反应。在这里，我们总结了CL在细胞信号通路中的作用，并关注心脏等高能量需求组织。CL最近被确定为脂质介质形成的前体。我们强调CL作为信号平台的概念。线粒体应激时，CL暴露于线粒体外膜，CL结构域在许多细胞信号事件中作为结合位点。在有丝分裂自噬过程中，CL与有丝分裂自噬的关键因子如Beclin 1相互作用，并通过与LC3的相互作用募集自噬机制。凋亡信号通路需要CL作为结合平台来募集凋亡因子，如tBid、Bax、半胱天冬酶-8。CL是炎性小体激活所必需的，并在炎症信号传导中发挥作用。由于在许多疾病中都观察到CL种类组成的变化，这里描述的信号通路可能在病理学中起普遍作用。
