Crosstalk between mitochondrial and lipid biogenesis

线粒体履行细胞生存力的各种基本功能。大量蛋白质和脂质的生物合成和输入对于线粒体的生物发生和功能至关重要。绝大多数线粒体蛋白质是在细胞质核糖体上作为前体合成的。两种线粒体膜的专用蛋白质移位酶将前体蛋白质转运到线粒体亚区室中。线粒体磷脂具有双重来源。一些磷脂如心磷脂在线粒体内合成。然而，大多数磷脂是在内质网（ER）中产生的，并通过细胞器接触位点输入线粒体。我们已经表明，个别磷脂差异影响线粒体蛋白质转位酶的功能和稳定性。我们的研究结果表明，脂质和蛋白质的生物合成必须紧密协调，然而，其机制尚不清楚。令人兴奋的是，我们发现了线粒体外膜蛋白转位酶，磷脂合成和细胞器接触位点之间的分子联系。该项目的目标是解开协调线粒体蛋白质和脂质生物合成的机制。我们将分析蛋白质转位酶和磷脂生物合成之间的分子联系在蛋白质插入线粒体外膜的作用。此外，我们将研究连接蛋白质运输和细胞器的蛋白质和脂质运输接触网站的生理作用。该项目将提供蛋白质-蛋白质相互作用如何调节线粒体蛋白质和脂质生物合成以满足生理需求的新见解。

Mitochondria fulfil various essential functions for cell viability. The biosynthesis and import of a large variety of proteins and lipids are crucial for mitochondrial biogenesis and functions. The vast majority of mitochondrial proteins are synthesized as precursors on cytosolic ribosomes. Dedicated protein translocases of both mitochondrial membranes transport precursor proteins into the mitochondrial subcompartments. Mitochondrial phospholipids are of dual origin. Some phospholipids such as cardiolipin are synthesized within mitochondria. However, the majority of phospholipids is produced in the endoplasmic reticulum (ER) and imported into mitochondria via organelle contact sites. We have shown that the individual phospholipids differentially affect function and stability of mitochondrial protein translocases. Our findings reveal that lipid and protein biogenesis have to be tightly coordinated, however, the mechanisms are unknown. Excitingly, we found a molecular connections between mitochondrial outer membrane protein translocases, phospholipid biosynthesis and organelle contact sites. The goal of this project is to unravel the mechanisms that coordinate mitochondrial protein and lipid biogenesis. We will analyse the role of the molecular link between protein translocases and phospholipid biosynthesis in protein insertion into the mitochondrial outer membrane. Furthermore, we will study the physiological role of connecting protein transport and organelle contact sites for protein and lipid transport. This project will deliver novel insights how protein-protein interactions adjust mitochondrial protein and lipid biogenesis to meet physiological demands.