Abstract
Author SummaryMitochondrial membrane biogenesis and lipid metabolism depend on the transfer of phospholipid from the endoplasmic reticulum to mitochondria. This transfer is thought to occur at regions where these organelles are in close contact, and, although the process is thought not to involve vesicles, the mechanism is not known. In this study, we found a complex of proteins in the endoplasmic reticulum that is required for the transfer of one phospholipid—phosphatidylserine—from the endoplasmic reticulum to mitochondria. Cells lacking this protein complex have nonfunctional mitochondria with an abnormal lipid composition. We show that the complex is required to maintain close contacts between the endoplasmic reticulum and mitochondria; the complex probably directly interacts with at least one protein on the surface of mitochondria. In addition, cells lacking this complex and a second previously identified tethering complex are not viable. Thus, our findings suggest that tethering of the endoplasmic reticulum and mitochondria is essential for cell growth, likely because it is necessary for lipid exchange between these organelles.
Highlights
Mitochondria are critical cellular components that are needed for energy production, lipid metabolism, calcium regulation, and apoptosis
We found that the growth defect of the Dpsd1Dcho2 mutant was rescued by the addition of ethanolamine or choline to the medium (Figure 1B), which allows cells to make PE and PC via the Kennedy pathway, indicating that this mutant had a defect in PE synthesis from PS (Figure 1A)
We reasoned that genes required for transfer of PS from endoplasmic reticulum (ER) to mitochondria and PE from mitochondria to ER would have negative genetic interactions with CHO2 that would be rescued by ethanolamine or choline
Summary
Mitochondria are critical cellular components that are needed for energy production, lipid metabolism, calcium regulation, and apoptosis. Phospholipid synthesis occurs largely in the endoplasmic reticulum (ER), and mitochondria acquire phospholipids from the ER at regions of close contact between these organelles [1,2,3]. Zones of close contact between organelles, often called membrane contact sites, are regions where lipids, small molecules, and other signals are transferred between organelles [4,5,6]. Contacts between the ER and mitochondria are important for lipid exchange and signaling between these organelles, but have been proposed to play a role in calcium signaling, apoptosis, Alzheimer’s disease pathology, and viral replication [7,8,9,10]
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