TY - JOUR
T1 - MIC OS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria
AU - Aaltonen, Mari J.
AU - Friedman, Jonathan R.
AU - Osman, Christof
AU - Salin, Bénédicte
AU - di Rago, Jean Paul
AU - Nunnari, Jodi
AU - Langer, Thomas
AU - Tatsuta, Takashi
N1 - Funding Information:
This work was supported by a grant of the Deutsche Forschungsgemeinschaft to T. Tatsuta and T. Langer (LA 918/14-1 and TA 1132/2-1) and a grant of the European Research Council to T. Langer (AdG No. 233078).
Publisher Copyright:
© 2016 Aaltonen et al.
PY - 2016
Y1 - 2016
N2 - Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRI AP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MIC OS). In MIC OS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MIC OS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.
AB - Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRI AP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MIC OS). In MIC OS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MIC OS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function.
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U2 - 10.1083/jcb.201602007
DO - 10.1083/jcb.201602007
M3 - Article
C2 - 27241913
AN - SCOPUS:84975230059
SN - 0021-9525
VL - 213
SP - 525
EP - 534
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -