Somerharju Pentti, Virtanen Jorma A, Hermansson Martin
Medicum Faculty of Medicine University of Helsinki Helsinki Finland.
Wihuri Research Institute Helsinki Finland.
FASEB Bioadv. 2020 Jan 27;2(3):182-187. doi: 10.1096/fba.2019-00058. eCollection 2020 Mar.
Mammalian cells maintain the complex glycerophospholipid (GPL) class compositions of their various membranes within close limits because this is essential to their well-being or viability. Surprisingly, however, it is still not understood how those compositions are maintained except that GPL synthesis and degradation are closely coordinated. Here, we hypothesize that abrupt changes in the chemical activity of the individual GPL classes coordinate synthesis and degradation as well other the homeostatic processes. We have previously proposed that only a limited number of "allowed" or "optimal" GPL class compositions exist in cellular membranes because those compositions are energetically more favorable than others, that is, they represent local free energy minima (Somerharju et al 2009, Biochim. Biophys. Acta 1788, 12-23). This model, however, could not satisfactorily explain how the "optimal" compositions are sensed by the key homeostatic enzymes, that is, rate-limiting synthetizing enzymes and homeostatic phospholipases. We now hypothesize that when the mole fraction of a GPL class exceeds an optimal value, its chemical activity abruptly increases which (a) increases its propensity to efflux from the membrane thus making it susceptible for hydrolysis by homeostatic phospholipases; (b) increases its potency to inhibit its own biosynthesis via a feedback mechanism; (c) enhances its conversion to another glycerophospholipid class via a novel process termed "head group remodeling" or (d) enhances its translocation to other subcellular membranes. In summary, abrupt change in the chemical activity of the individual GPL classes is proposed to regulate and coordinate those four processes maintaining GPL class homeostasis in mammalian cells.
哺乳动物细胞将其各种膜的复杂甘油磷脂（GPL）类组成维持在很窄的范围内，因为这对其健康或生存能力至关重要。然而，令人惊讶的是，除了GPL合成和降解密切协调外，人们仍然不了解这些组成是如何维持的。在这里，我们假设单个GPL类的化学活性的突然变化协调了合成和降解以及其他稳态过程。我们之前曾提出，细胞膜中只存在有限数量的“允许”或“最佳”GPL类组成，因为这些组成在能量上比其他组成更有利，也就是说，它们代表局部自由能最小值（Somerharju等人，2009年，《生物化学与生物物理学报》1788，12 - 23）。然而，该模型无法令人满意地解释关键稳态酶，即限速合成酶和稳态磷脂酶是如何感知“最佳”组成的。我们现在假设，当一个GPL类的摩尔分数超过最佳值时，其化学活性会突然增加，这（a）增加了其从膜中流出的倾向，从而使其易于被稳态磷脂酶水解；（b）通过反馈机制增加了其抑制自身生物合成的能力；（c）通过一个称为“头部基团重塑”的新过程增强其向另一种甘油磷脂类的转化；或（d）增强其向其他亚细胞膜的转运。总之，单个GPL类的化学活性的突然变化被认为可以调节和协调这四个维持哺乳动物细胞中GPL类稳态的过程。
