Mechanisms of intramitochondrial lipid traffic by Ups/PRELI lipid transfer proteins
Mari Aaltonen1, Thomas Langer1, 2, Takashi Tatsuta1, 2
1Institute of Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany
2 Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
Mitochondrial functions and architecture rely on a defined lipid composition of their outer and inner membranes, which are characterized by a high content of non-bilayer phospholipids such as cardiolipin (CL) and phosphatidylethanolamine (PE). Mitochondrial membrane lipids are synthesized in the endoplasmic reticulum (ER) or within mitochondria from ER-derived precursor lipids, are asymmetrically distributed within mitochondria and can relocate in response to cellular stress. Maintenance of lipid homeostasis thus requires multiple lipid transport processes to be orchestrated within mitochondria which relies on the functions of Ups/PRELI family of lipid transfer proteins. Multiple members of Ups/PRELI proteins reside in the intermembrane space of mitochondria and shuttle phospholipids between mitochondrial membranes in a specific manner. They cooperate with membrane organizing proteins that preserve the spatial organization of mitochondrial membranes and the formation of membrane contact sites, unravelling an intimate crosstalk of membrane lipid transport and homeostasis with the structural organization of mitochondria. Underlying mechanisms ensure regulated traffic of specific lipids and their accessibility by lipid-synthesizing enzymes, which are dependent on Ups/PRELI and membrane organizing protein machineries, will be discussed.
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