Long-lived mitochondrial cristae proteins in mouse heart and brain

2021 ◽  
Vol 220 (9) ◽  
Author(s):  
Ewa Bomba-Warczak ◽  
Seby L. Edassery ◽  
Timothy J. Hark ◽  
Jeffrey N. Savas
Keyword(s):  
Mitochondrial Membrane ◽  
Isotope Labeling ◽  
Mitochondrial Protein ◽  
Cross Linking ◽  
Mouse Heart ◽  
Inner Mitochondrial Membrane ◽  
Subunit Exchange ◽  
Mitochondrial Proteome ◽  
Long Term Stability

Long-lived proteins (LLPs) have recently emerged as vital components of intracellular structures whose function is coupled to long-term stability. Mitochondria are multifaceted organelles, and their function hinges on efficient proteome renewal and replacement. Here, using metabolic stable isotope labeling of mice combined with mass spectrometry (MS)–based proteomic analysis, we demonstrate remarkable longevity for a subset of the mitochondrial proteome. We discovered that mitochondrial LLPs (mt-LLPs) can persist for months in tissues harboring long-lived cells, such as brain and heart. Our analysis revealed enrichment of mt-LLPs within the inner mitochondrial membrane, specifically in the cristae subcompartment, and demonstrates that the mitochondrial proteome is not turned over in bulk. Pioneering cross-linking experiments revealed that mt-LLPs are spatially restricted and copreserved within protein OXPHOS complexes, with limited subunit exchange throughout their lifetimes. This study provides an explanation for the exceptional mitochondrial protein lifetimes and supports the concept that LLPs provide key structural stability to multiple large and dynamic intracellular structures.

scholarly journals mtCLIC/CLIC4, an Organellular Chloride Channel Protein, Is Increased by DNA Damage and Participates in the Apoptotic Response to p53

2002 ◽  
Vol 22 (11) ◽  
pp. 3610-3620 ◽  
Author(s):  
Ester Fernández-Salas ◽  
Kwang S. Suh ◽  
Vladislav V. Speransky ◽  
Wendy L. Bowers ◽  
Joshua M. Levy ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Mitochondrial Membrane ◽  
Cellular Response ◽  
Mitochondrial Protein ◽  
Inner Mitochondrial Membrane ◽  
Necrosis Factor Alpha ◽  
Channel Protein ◽  
Factor Alpha

ABSTRACT mtCLIC/CLIC4 (referred to here as mtCLIC) is a p53- and tumor necrosis factor alpha-regulated cytoplasmic and mitochondrial protein that belongs to the CLIC family of intracellular chloride channels. mtCLIC associates with the inner mitochondrial membrane. Dual regulation of mtCLIC by two stress response pathways suggested that this chloride channel protein might contribute to the cellular response to cytotoxic stimuli. DNA damage or overexpression of p53 upregulates mtCLIC and induces apoptosis. Overexpression of mtCLIC by transient transfection reduces mitochondrial membrane potential, releases cytochrome c into the cytoplasm, activates caspases, and induces apoptosis. mtCLIC is additive with Bax in inducing apoptosis without a physical association of the two proteins. Antisense mtCLIC prevents the increase in mtCLIC levels and reduces apoptosis induced by p53 but not apoptosis induced by Bax, suggesting that the two proapoptotic proteins function through independent pathways. Our studies indicate that mtCLIC, like Bax, Noxa, p53AIP1, and PUMA, participates in a stress-induced death pathway converging on mitochondria and should be considered a target for cancer therapy through genetic or pharmacologic approaches.

scholarly journals Novel blood protein based scaffolds for cardiovascular tissue engineering

2016 ◽  
Vol 2 (1) ◽  
pp. 5-9 ◽  
Author(s):  
Antonia I. Kuhn ◽  
Marc Müller ◽  
Sara Knigge ◽  
Birgit Glasmacher
Keyword(s):  
Tissue Engineering ◽  
Fibre Diameter ◽  
Final Concentration ◽  
Blood Protein ◽  
Cross Linking ◽  
Blood Proteins ◽  
Cardiovascular Tissue ◽  
Long Term Stability ◽  
Cardiovascular Tissue Engineering

AbstractA major challenge in cardiovascular tissue engineering is the fabrication of scaffolds, which provide appropriate morphological and mechanical properties while avoiding undesirable immune reactions. In this study electrospinning was used to fabricate scaffolds out of blood proteins for cardiovascular tissue engineering. Lyophilised porcine plasma was dissolved in deionised water at a final concentration of 7.5% m/v and blended with 3.7% m/v PEO. Electrospinning resulted in homogeneous fibre morphologies with a mean fibre diameter of 151 nm, which could be adapted to create macroscopic shapes (mats, tubes). Cross-linking with glutaraldehyde vapour improved the long-term stability of protein based scaffolds in comparison to untreated scaffolds, resulting in a mass loss of 41% and 96% after 28 days of incubation in aqueous solution, respectively.

scholarly journals Corneal Cross-Linking for Progressive Keratoconus in Children: Our Experience

2012 ◽  
Vol 1 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Erez Bakshi ◽  
Yaniv Barkana ◽  
Yakov Goldich ◽  
Isaac Avni ◽  
David Zadok
Keyword(s):  
Visual Acuity ◽  
Medical Center ◽  
Statistical Significance ◽  
Cross Linking ◽  
Long Term Stability ◽  
Corrected Visual Acuity ◽  
Department Of Ophthalmology ◽  
Manifest Refraction ◽  
Uncorrected Visual Acuity

ABSTRACT Purpose To assess the effect of corneal cross-linking on progressive keratoconus in children. Method In this retrospective study we enrolled nine eyes of nine consecutive children aged 11 to 17 years old who underwent corneal riboflavin-UVA induced cross-linking for progressive keratoconus at the Department of Ophthalmology at Assaf Harofeh Medical Center. They were followed for 6 to 24 months (average 16 ± 8.1 months). Evaluated parameters were uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), manifest refraction, pachymetry, slit lamp examination and corneal topography. Results Cross-linking resulted in stability of visual acuity in seven of the nine (77.8%) treated eyes. We found a nonsignificant improvement in UCVA and BSCVA with a small reduction of manifest cylinder. Furthermore, there was an improvement in spherical equivalent that was close to statistical significance (p = 0.07). There was 0.86 D reduction of average Kmax value postoperatively (p = 0.36). Most patients (7 of 9, 77.8%) showed a long-term stability or reduction in Kmax. Conclusion In this study, we demonstrated the efficacy of corneal cross-linking in arresting the progression of keratoconus in children. We believe that larger scale studies in this age group should be performed to further establish the relevance of this technique in children. How to cite this article Bakshi E, Barkana Y, Goldich Y, Avni I, Zadok D. Corneal Cross-Linking for Progressive Keratoconus in Children Our Experience. Int J Keratoco Ectatic Corneal Dis 2012;1(1):53-56.

scholarly journals Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2147
Author(s):  
Bruno Seitaj ◽  
Felicia Maull ◽  
Li Zhang ◽  
Verena Wüllner ◽  
Christina Wolf ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Structure ◽  
Protein Synthesis Machinery ◽  
Atp Generation ◽  
And Function

The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson’s disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.

scholarly journals The study of cell-death proteins in the outer mitochondrial membrane by chemical cross-linking

1997 ◽  
Vol 325 (2) ◽  
pp. 321-324 ◽  
Author(s):  
Sohail T. ALI ◽  
John R. COGGINS ◽  
Howard T. JACOBS
Keyword(s):  
Cell Death ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Surface Proteins ◽  
Cross Linking ◽  
Outer Mitochondrial Membrane ◽  
Cross Link ◽  
Cell Death Protein ◽  
Chemical Cross Linking

Chemical cross-linking was used to study the interactions of the anti-cell-death protein Bcl2 with other proteins in the outer mitochondrial membrane. Cross-linking of mitochondrial surface proteins produced a large Bcl2-containing complex (> 200 kDa), and a Bcl2-derived peptide was shown to cross-link specifically with a mitochondrial protein identified by immunoblotting as Raf-1 kinase.

Molecular interactions of Bipolaris maydis T-toxin and maize

1995 ◽  
Vol 73 (S1) ◽  
pp. 483-489 ◽  
Author(s):  
Charles S. Levings III ◽  
David M. Rhoads ◽  
James N. Siedow
Keyword(s):  
Male Sterility ◽  
Mitochondrial Membrane ◽  
Fungal Pathogens ◽  
Mitochondrial Gene ◽  
Site Directed Mutagenesis ◽  
Cross Linking ◽  
Male Sterile ◽  
Inner Mitochondrial Membrane ◽  
Bipolaris Maydis ◽  
Maize Cytoplasmic Male Sterility

The toxins (T-toxins) produced by the fungal pathogens Bipolaris maydis race T (BmT) and Phyllosticta maydis (Pm) target the mitochondrial receptor, URF13, in maize (Zea mays L.) plants containing the Texas male-sterile cytoplasm (cms-T). URF13, a 13-kDa protein, is the product of the maize mitochondrial gene T-urf13, which is found only in the mitochondrial genome of cms-T maize and is thought to be responsible for cytoplasmically inherited male sterility and disease susceptibility. Pm-toxin binds specifically to URF13 in a cooperative manner, and Pm- and BmT-toxins compete for the same, or overlapping, binding sites. The binding of T-toxin to URF13 causes rapid permcabilization of the inner mitochondrial membrane, which results in leakage of NAD+ and other ions from the matrix. A pore consisting of at least six transmembrane α-helices is required for NAD+ leakage. Cross-linking experiments showed that URF13 oligomers are present in the mitochondrial membrane. A model of the secondary structure of URF13 proposes that each monomer contains three transmembrane α-helices. Studies combining site-directed mutagenesis and chemical cross-linking of URF13 expressed by Escherichia coli cells indicate that the oligomers are composed of a central core of helices II that line the center of the URF13 pores. Key words: maize cytoplasmic male sterility, URF13, mitochondrial pores, T-toxin receptor, Bipolaris maydis race T, Phyllosticta maydis, Helminthosporium maydis.

Bilateral, Asymmetric Keratoconus Induced by Thyrotoxicosis With Long-term Stability After Corneal Cross-linking

2018 ◽  
Vol 34 (5) ◽  
pp. 354-356 ◽  
Author(s):  
Ramon Lee ◽  
Ahmed El-Massry ◽  
Youssef El-Massry ◽  
J. Bradley Randleman
Keyword(s):  
Cross Linking ◽  
Term Stability ◽  
Long Term Stability

scholarly journals Evidence of the Proximity of ATP Synthase Subunits 6 (a) in the Inner Mitochondrial Membrane and in the Supramolecular Forms of Saccharomyces cerevisiae ATP Synthase

2011 ◽  
Vol 286 (41) ◽  
pp. 35477-35484 ◽  
Author(s):  
Jean Velours ◽  
Claire Stines-Chaumeil ◽  
Johan Habersetzer ◽  
Stéphane Chaignepain ◽  
Alain Dautant ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Transmembrane Helix ◽  
Disulfide Bridge ◽  
Cross Linking ◽  
Null Mutant ◽  
Terminal Part ◽  
Inner Mitochondrial Membrane ◽  
Membrane Spanning

The involvement of subunit 6 (a) in the interface between yeast ATP synthase monomers has been highlighted. Based on the formation of a disulfide bond and using the unique cysteine 23 as target, we show that two subunits 6 are close in the inner mitochondrial membrane and in the solubilized supramolecular forms of the yeast ATP synthase. In a null mutant devoid of supernumerary subunits e and g that are involved in the stabilization of ATP synthase dimers, ATP synthase monomers are close enough in the inner mitochondrial membrane to make a disulfide bridge between their subunits 6, and this proximity is maintained in detergent extract containing this enzyme. The cross-linking of cysteine 23 located in the N-terminal part of the first transmembrane helix of subunit 6 suggests that this membrane-spanning segment is in contact with its counterpart belonging to the ATP synthase monomer that faces it and participates in the monomer-monomer interface.

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