Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, Université de Paris, LBPC-PM, CNRS, UMR7099, 75005, Paris, France.
Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild pour le Développement de la Recherche Scientifique, 75005, Paris, France.
Microb Cell Fact. 2020 Sep 4;19(1):176. doi: 10.1186/s12934-020-01433-x.
Membrane remodeling and phospholipid biosynthesis are normally tightly regulated to maintain the shape and function of cells. Indeed, different physiological mechanisms ensure a precise coordination between de novo phospholipid biosynthesis and modulation of membrane morphology. Interestingly, the overproduction of certain membrane proteins hijack these regulation networks, leading to the formation of impressive intracellular membrane structures in both prokaryotic and eukaryotic cells. The proteins triggering an abnormal accumulation of membrane structures inside the cells (or membrane proliferation) share two major common features: (1) they promote the formation of highly curved membrane domains and (2) they lead to an enrichment in anionic, cone-shaped phospholipids (cardiolipin or phosphatidic acid) in the newly formed membranes. Taking into account the available examples of membrane proliferation upon protein overproduction, together with the latest biochemical, biophysical and structural data, we explore the relationship between protein synthesis and membrane biogenesis. We propose a mechanism for the formation of these non-physiological intracellular membranes that shares similarities with natural inner membrane structures found in α-proteobacteria, mitochondria and some viruses-infected cells, pointing towards a conserved feature through evolution. We hope that the information discussed in this review will give a better grasp of the biophysical mechanisms behind physiological and induced intracellular membrane proliferation, and inspire new applications, either for academia (high-yield membrane protein production and nanovesicle production) or industry (biofuel production and vaccine preparation).
膜重塑和磷脂生物合成通常受到严格调控，以维持细胞的形状和功能。事实上，不同的生理机制确保了新合成的磷脂生物合成与膜形态调节之间的精确协调。有趣的是，某些膜蛋白的过度表达会劫持这些调节网络，导致原核和真核细胞中形成令人印象深刻的细胞内膜结构。触发细胞内膜结构异常积累（或膜增殖）的蛋白质具有两个主要共同特征：（1）它们促进高度弯曲的膜域的形成，（2）它们导致新形成的膜中阴离子、锥形磷脂（心磷脂或磷脂酸）的富集。考虑到蛋白质过度表达时膜增殖的现有实例，以及最新的生化、生物物理和结构数据，我们探讨了蛋白质合成与膜生物发生之间的关系。我们提出了一种形成这些非生理细胞内膜的机制，该机制与α-变形菌、线粒体和一些感染病毒的细胞中发现的天然内膜结构具有相似之处，这表明在进化过程中存在保守特征。我们希望本综述中讨论的信息将有助于更好地理解生理和诱导的细胞内膜增殖背后的生物物理机制，并为学术界（高产膜蛋白生产和纳米囊泡生产）或工业界（生物燃料生产和疫苗制备）提供新的应用。
