MICOS and phospholipid transfer by Ups2–Mdm35 organize membrane lipid synthesis in mitochondria

• DOI: 10.1083/jcb.201602007
• Publication Date: 2016-05-30T14:13:36Z
• Authors: Mari J. Aaltonen; Jonathan R. Friedman; Christof Osman; Bénédicte Salin; Jean-Paul di Rago; Jodi Nunnari; Thomas Langer; Takashi Tatsuta
• Keywords: 0301 basic medicine; 570; Biomedical and clinical sciences; Saccharomyces cerevisiae Proteins; 1.1 Normal biological development and functioning; Phosphatidylserines; Saccharomyces cerevisiae; Endoplasmic Reticulum; Medical and Health Sciences; Mitochondrial Proteins; Membrane Lipids; 03 medical and health sciences; Underpinning research; Research Articles; Phospholipids; Phosphatidylethanolamines; ddc:no; Biological Sciences; Mitochondria; Biological sciences; Protein Subunits; Mitochondrial Membranes; Phosphatidylcholines; Biochemistry and Cell Biology; Generic health relevance; Gene Deletion; Developmental Biology

Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents membranes, such as phosphatidylethanolamine (PE) phosphatidylcholine. Here, we demonstrate that phosphatidylserine decarboxylase Psd1, located inner mitochondrial membrane, promotes PE via two pathways. First, Ups2–Mdm35 complexes (SLMO2–TRIAP1 humans) serve (PS)-specific transfer proteins intermembrane space, allowing formation by Psd1 membrane. Second, decarboxylates PS outer membrane trans, independently Ups2–Mdm35. This latter pathway requires close apposition between both membranes contact site cristae organizing system (MICOS). In MICOS-deficient cells, limiting reducing accumulation preserves respiration formation. These results link to MICOS, combining protein homeostasis preserve structure function.