title: Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria.
abstract: Two protein translocases transport precursor proteins into or across the inner mitochondrial membrane. The presequence translocase (TIM23 complex) sorts precursor proteins with a cleavable presequence either into the matrix or into the inner membrane. The carrier translocase (TIM22 complex) inserts multispanning proteins into the inner membrane. Both protein import pathways depend on the presence of a membrane potential, which is generated by the activity of the respiratory chain. The non-bilayer-forming phospholipids cardiolipin and phosphatidylethanolamine are required for the activity of the respiratory chain and therefore to maintain the membrane potential for protein import. Depletion of cardiolipin further affects the stability of the TIM23 complex. The role of bilayer-forming phospholipids like phosphatidylcholine (PC) in protein transport into the inner membrane and the matrix is unknown. Here, we report that import of presequence-containing precursors and carrier proteins is impaired in PC-deficient mitochondria. Surprisingly, depletion of PC does not affect stability and activity of respiratory supercomplexes, and the membrane potential is maintained. Instead, the dynamic TIM23 complex is destabilized when the PC levels are reduced, whereas the TIM22 complex remains intact. Our analysis further revealed that initial precursor binding to the TIM23 complex is impaired in PC-deficient mitochondria. We conclude that reduced PC levels differentially affect the TIM22 and TIM23 complexes in mitochondrial protein transport.
authors.affiliation: From the Institute for Biochemistry and Molecular Biology, Faculty of Medicine.
authors.forename: Max-Hinderk
authors.initials: MH
authors.lastname: Schuler
authors.affiliation: the Institute for Biochemistry, Graz University of Technology, NaWi Graz, A-8010 Graz, Austria.
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Bartolomeo
authors.affiliation: From the Institute for Biochemistry and Molecular Biology, Faculty of Medicine, Faculty of Biology, and.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Mårtensson
authors.affiliation: the Institute for Biochemistry, Graz University of Technology, NaWi Graz, A-8010 Graz, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Daum
authors.affiliation: From the Institute for Biochemistry and Molecular Biology, Faculty of Medicine, BIOSS Centre for Biological Signalling Studies, University of Freiburg, D-79104 Freiburg, Germany and thomas.becker@biochemie.uni-freiburg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
mesh_terms: D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010713:Phosphatidylcholines / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D010713:Phosphatidylcholines; D029701:Saccharomyces cerevisiae Proteins; C102549:TIM22 protein, S cerevisiae; C083081:TIM23 protein, S cerevisiae
keywords: TIM22 complex; TIM23 complex; mitochondria; phosphatidylcholine; protein complex; protein sorting; protein translocation; respiratory chain