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

Schuler, Max‐Hinderk; Bartolomeo, Francesca Di; Böttinger, Lena; Horvath, Susanne E.; Wenz, Lena‐Sophie; Daum, Günther; Becker, Thomas

doi:10.1074/jbc.m115.687921

Cited by 28 publications

(30 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, the TOM complex remains intact in PC-deficient mitochondria (Fig. 5D) (75). We conclude that depletion of PC affects initial recognition of the precursor by the TIM23 complex.…”

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 64%

“…However, the accumulation of TIM23-dependent precursors like Om45-DHFR (81,82) and Oxa1 at the TOM complex was not decreased (Fig. 6B) (75). Furthermore, the TOM complex remains intact in PC-deficient mitochondria (Fig.…”

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 89%

“…Depletion of PC selectively affects the stability of highly dynamic protein translocases like the TIM23 complex of the inner membrane and the sorting and assembly machinery (SAM complex) of the outer membrane (75). The SAM complex mediates folding and insertion of ␤-barrel proteins in the mitochondrial outer membrane (3-5, 7, 8).…”

Section: Discussionmentioning

confidence: 99%

“…Notably, the steady state levels of Tim10 were largely unaffected in these mutant mitochondria as well (Fig. 5A) (75). Small TIM chaperones like Tim10 are essential for transport of carrier precursors through the intermembrane space to the TIM22 translocase (22,23).…”

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 93%

“…PC is essential for the survival of the cell (72). Recent studies revealed that yeast cells with decreased PC levels show a reduced growth under non-fermentative conditions and that the biogenesis of outer membrane ␤-barrel and some ␣-helical proteins is impaired in mitochondria isolated from these cells (75). The role of PC in protein transport into the inner mitochondrial subcompartments is unknown.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Schuler¹,

Bartolomeo

Mårtensson

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

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 ...

show abstract

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 64%

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Depletion Of Pc Impairs Protein Transport Into the Innermentioning

confidence: 93%

mentioning

confidence: 99%

See 3 more Smart Citations

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Schuler¹,

Bartolomeo

Mårtensson

et al. 2016

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond

2023

View full text Add to dashboard Cite

Mitochondria hold diverse and pivotal roles in fundamental processes that govern cell survival, differentiation, and death, in addition to organismal growth, maintenance, and aging. The mitochondrial protein import system is a major contributor to mitochondrial biogenesis and lies at the crossroads between mitochondrial and cellular homeostasis. Recent findings highlight the mitochondrial protein import system as a signaling hub, receiving inputs from other cellular compartments and adjusting its function accordingly. Impairment of protein import, in a physiological, or disease context, elicits adaptive responses inside and outside mitochondria. In this review, we discuss recent developments, relevant to the mechanisms of mitochondrial protein import regulation, with a particular focus on quality control, proteostatic and metabolic cellular responses, triggered upon impairment of mitochondrial protein import. K E Y W O R D Smetabolism, mitochondrial protein import, mitochondrial unfolded protein response, mitophagy, proteostasis Recent findings from system biology studies in whole cells (in vivo) have highlighted the mitochondrial protein import system as a critical

show abstract

Endoplasmic reticulum stress and calcium imbalance are involved in cadmium-induced lipid aberrancy in Saccharomyces cerevisiae

Rajakumar

Bhanupriya

Ravi

2016

Cell Stress and Chaperones

View full text Add to dashboard Cite

The endoplasmic reticulum is the key organelle which controls protein folding, lipid biogenesis, and calcium (Ca 2+ ) homeostasis. Cd exposure in Saccharomyces cerevisiae activated the unfolded protein response and was confirmed by the increased Kar2p expression. Cd exposure in wild-type (WT) cells increased PC levels and the PC biosynthetic genes. Deletion of the two phospholipid methyltransferases CHO2 and OPI3 modulated PC, TAG levels and the lipid droplets with cadmium exposure. Interestingly, we noticed an increase in the calcium levels upon Cd exposure in the mutant cells. This study concluded that Cd interrupted calcium homeostasis-induced lipid dysregulation leading to ER stress.

show abstract

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

Cited by 28 publications

References 89 publications

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

Mitochondrial protein import machinery conveys stress signals to the cytosol and beyond

Endoplasmic reticulum stress and calcium imbalance are involved in cadmium-induced lipid aberrancy in Saccharomyces cerevisiae

Contact Info

Product

Resources

About