A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex

Song, Jiyao; Tamura, Yasushi; Yoshihisa, Tohru; Endo, Toshiya

doi:10.1002/embr.201338142

Cited by 33 publications

(43 citation statements)

References 20 publications

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“…assembled into the outer membrane (81,88). Therefore, the transport of this precursor across the TOM complex was not impaired in PC-deficient mitochondria (Fig.…”

Section: Biogenesis Of the Mitochondrial Outer Membranementioning

confidence: 90%

Phosphatidylcholine Affects the Role of the Sorting and Assembly Machinery in the Biogenesis of Mitochondrial β-Barrel Proteins

Schuler

Bartolomeo

Böttinger

et al. 2015

Journal of Biological Chemistry

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“…assembled into the outer membrane (81,88). Therefore, the transport of this precursor across the TOM complex was not impaired in PC-deficient mitochondria (Fig.…”

Section: Biogenesis Of the Mitochondrial Outer Membranementioning

confidence: 90%

Phosphatidylcholine Affects the Role of the Sorting and Assembly Machinery in the Biogenesis of Mitochondrial β-Barrel Proteins

Schuler

Bartolomeo

Böttinger

et al. 2015

Journal of Biological Chemistry

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“…One possibility is that the reduced PC levels affect the function of the TOM complex. However, the accumulation of TIM23-dependent precursors like Om45-DHFR (81,82) and Oxa1 at the TOM complex was not decreased (Fig. 6B) (75).…”

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 92%

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Schuler¹,

Bartolomeo

Mårtensson

et al. 2016

Journal of Biological Chemistry

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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.Mitochondria fulfill essential functions for the survival of the cell like energy conversion to produce ATP, synthesis of amino acids, lipids, and heme, as well as the generation of iron-sulfur clusters. They contain about 1000 proteins in yeast and 1500 proteins in humans (1, 2). More than 99% of the mitochondrial proteins are synthesized as precursors on cytosolic ribosomes. Mitochondria contain a sophisticated system of protein translocases to import precursor proteins (3-9). The translocase of the outer membrane (TOM 3 complex) forms the general entry gate for most precursor proteins. After passage of the TOM channel, distinct protein translocases sort the preproteins into the different subcompartments: the outer and inner membrane as well as the two aqueous compartments, the matrix and intermembrane space.The majority of mitochondrial proteins are sorted into the inner membrane and the matrix. Two inner membrane-bound protein complexes mediate protein import. The presequence translocase (also termed TIM23 complex) transports precursor proteins with a cleavable presequence into the inner membrane and the matrix, whereas the carrier translocase (also termed TIM22 complex) inserts proteins with multiple transmembrane segments into the inner membrane (3-9). The membrane potential across the inner membrane provides the driving force for both protein import pathways and is generated by the activity of the respiratory chain. Presequence-containing preproteins are directly transferred from the ...

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“…Of note, also all experiments set out to detect a potential interaction of Om45 with Aim19 lead to negative results (data not shown). Interestingly, Mcp3 and Om45 share some similarities in their biogenesis pathway, in that they are the only integral MOM proteins known that rely for their import on the inner mitochondrial import machinery TIM23 complex and on the mitochondrial membrane potential .…”

Section: Resultsmentioning

confidence: 99%

Interaction network of the mitochondrial outer membrane protein Mcp3

2018

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Mitochondria are organelles containing two membranes that are distinct in composition and function. A role of the mitochondrial outer membrane (MOM) is to mediate contact of the organelle with the rest of the cell. In yeast, the MOM contains about 40 different integral proteins. Recently, we described the MOM protein Mcp3, which can serve as a multicopy suppressor of loss of ERMES complex that mediates mitochondria-endoplasmic reticulum contacts. To shed further light on the role of Mcp3 in the MOM, we analyzed its physical interaction with other proteins. We show that Mcp3 interacts with the MOM protein Om45 and the inner membrane protein Aim19. Our observations hint toward a potential involvement of Mcp3 in a structural and/or functional link between both mitochondrial membranes.

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A novel import route for an N-anchor mitochondrial outer membrane protein aided by the TIM23 complex

Cited by 33 publications

References 20 publications

Phosphatidylcholine Affects the Role of the Sorting and Assembly Machinery in the Biogenesis of Mitochondrial β-Barrel Proteins

Phosphatidylcholine Affects the Role of the Sorting and Assembly Machinery in the Biogenesis of Mitochondrial β-Barrel Proteins

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Interaction network of the mitochondrial outer membrane protein Mcp3

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