Role of membrane contact sites in protein import into mitochondria

Horvath, Susanne E.; Rampelt, Heike; Oeljeklaus, Silke; Warscheid, Bettina; Laan, Martin van der; Pfanner, Nikolaus

doi:10.1002/pro.2625

Cited by 55 publications

(38 citation statements)

References 289 publications

(585 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed that CL, a key mitochondrial lipid, is dramatically reduced in the brains of GW agent exposed mice. Cardiolipin represents 20% of total mitochondrial lipids (Horvath et al, 2015) and a reduction in CL is a strong indicator of decreased activity of the electron transport chain (ETC) (Shen et al, 2015). Mitochondrial bioenergetics rely on adequate quantities of CL and a reduction of CL suggests impaired ATP production.…”

Section: Discussionmentioning

confidence: 99%

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness

et al. 2016

View full text Add to dashboard Cite

Gulf War Illness (GWI) affects 25% of veterans from the 1990-1991 Gulf War (GW) and is accompanied by damage to the brain regions involved in memory processing. After twenty-five years, the chronic pathobiology of GWI is still unexplained. To address this problem, we examined the long-term consequences of GW exposures in an established GWI mouse model to identify biological processes that are relevant to the chronic symptoms of GWI. Three-month old male C57BL6 mice were exposed for 10days to GW agents (pyridostigmine bromide and permethrin). Barnes Maze testing conducted at 15- and 16-months post-exposure revealed learning and memory impairment. Immunohistochemical analyses showed astroglia and microglia activation in the hippocampi of exposed mice. Proteomic studies identified perturbation of mitochondria function and metabolomics data showed decreases in the Krebs cycle compounds, lactate, β-hydroxybutyrate and glycerol-3 phosphate in the brains of exposed mice. Lipidomics data showed decreases in fatty acids, acylcarnitines and phospholipids, including cardiolipins in the brains of exposed mice. Pilot biomarker studies showed that plasma from exposed mice and veterans with GWI had increases in odd-chain, and decreases in long-chain, acylcarnitines compared to their respective controls. Very long-chain acylcarnitines were decreased in veterans with GWI compared to controls. These studies suggest that mitochondrial lipid disturbances might be associated with GWI and that further investigation is required to determine its role in the pathophysiology of this illness. Targeting mitochondrial function may provide effective therapies for GWI, and that lipid abnormalities could serve as biomarkers of GWI.

show abstract

Section: Discussionmentioning

confidence: 99%

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This increases numbers of predicted peptides to extents that, for unbiased analyses, are incompatible with current computing capacities. For these reasons, previous and current analyses have been restricted to peptides encoded by the human mitogenome, excluding nucleus-encoded mitochondrial proteins, which are imported from the cytosol into the mitochondrion [149], [150], [151], [152].…”

Section: Discussionmentioning

confidence: 99%

Unbiased Mitoproteome Analyses Confirm Non-canonical RNA, Expanded Codon Translations

Seligmann

2016

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Proteomic MS/MS mass spectrometry detections are usually biased towards peptides cleaved by experimentally added digestion enzyme(s). Hence peptides resulting from spontaneous degradation and natural proteolysis usually remain undetected. Previous analyses of tryptic human proteome data (cleavage after K, R) detected non-canonical tryptic peptides translated according to tetra- and pentacodons (codons expanded by silent mono- and dinucleotides), and from transcripts systematically (a) deleting mono-, dinucleotides after trinucleotides (delRNAs), (b) exchanging nucleotides according to 23 bijective transformations. Nine symmetric and fourteen asymmetric nucleotide exchanges (X ↔ Y, e.g. A ↔ C; and X → Y → Z → X, e.g. A → C → G → A) produce swinger RNAs. Here unbiased reanalyses of these proteomic data detect preferentially non-canonical tryptic peptides despite assuming random cleavage. Unbiased analyses couldn't reconstruct experimental tryptic digestion if most detected non-canonical peptides were false positives. Detected non-tryptic non-canonical peptides map preferentially on corresponding, previously described non-canonical transcripts, as for tryptic non-canonical peptides. Hence unbiased analyses independently confirm previous trypsin-biased analyses that showed translations of del- and swinger RNA and expanded codons. Accounting for natural proteolysis completes trypsin-biased mitopeptidome analyses, independently confirms non-canonical transcriptions and translations.

show abstract

“…Contact sites between the mitochondrial outer and inner membranes are not only formed via the MICOS complex, but several more dynamic contact structures have been reported (summarized in Reichert and Neupert, 2002;van der Laan et al, 2012;Horvath et al, 2015). With regard to protein translocases, the TOM-TIM23 supercomplex forms an important contact site.…”

Section: Protein Translocases and Mitochondrial Architecturementioning

confidence: 99%

Dynamic organization of the mitochondrial protein import machinery

Straub

Stiller

Wiedemann

et al. 2016

Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Mitochondria contain elaborate machineries for the import of precursor proteins from the cytosol. The translocase of the outer mitochondrial membrane (TOM) performs the initial import of precursor proteins and transfers the precursors to downstream translocases, including the presequence translocase and the carrier translocase of the inner membrane, the mitochondrial import and assembly machinery of the intermembrane space, and the sorting and assembly machinery of the outer membrane. Although the protein translocases can function as separate entities in vitro, recent studies revealed a close and dynamic cooperation of the protein import machineries to facilitate efficient transfer of precursor proteins in vivo. In addition, protein translocases were found to transiently interact with distinct machineries that function in the respiratory chain or in the maintenance of mitochondrial membrane architecture. Mitochondrial protein import is embedded in a regulatory network that ensures protein biogenesis, membrane dynamics, bioenergetic activity and quality control.

show abstract

Role of membrane contact sites in protein import into mitochondria

Cited by 55 publications

References 289 publications

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness

Translational potential of long-term decreases in mitochondrial lipids in a mouse model of Gulf War Illness

Unbiased Mitoproteome Analyses Confirm Non-canonical RNA, Expanded Codon Translations

Dynamic organization of the mitochondrial protein import machinery

Contact Info

Product

Resources

About