Regulation of the protein disulfide proteome by mitochondria in mammalian cells

Yang, Yi; Song, Yuanyuan; Loscalzo, Joseph

doi:10.1073/pnas.0702027104

Cited by 119 publications

(109 citation statements)

References 27 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…The Env folding involves cross-linking of 20 cysteine residues, which is dependent on heavy N-glycosylation and the most oxidizing redox status in the ER (31). It has been suggested that the oxidative protein folding in the ER is controlled by mitochondria, likely via regulating the ER redox status through releasing reactive oxygen species (32). Intracellular reactive oxygen species is mainly produced by mitochondria as a byproduct from energy production.…”

Section: Discussionmentioning

confidence: 99%

ERManI (Endoplasmic Reticulum Class I α-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway

Zhou

Frabutt

Moremen

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: HIV-1 envelope (Env) glycoprotein is targeted to endoplasmic reticulum (ER)-associated protein degradation (ERAD) pathway for degradation after infecting cells. Results: ER class I ␣-mannosidase (ERManI) interacts with Env and initiates this degradation process. Conclusion: ERManI is essential for the Env degradation. Significance: These findings define a novel endogenous and potential therapeutically applicable antiretroviral mechanism by targeting Env for degradation.

show abstract

Section: Discussionmentioning

confidence: 99%

ERManI (Endoplasmic Reticulum Class I α-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway

Zhou

Frabutt

Moremen

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…However, an emerging concept identifies two types of disulfide bonds, a structural group and a redox-sensitive regulatory group, with the latter having direct functional consequences for the cell [27,28]. After bacterial transcription factor OxyR was found to be directly activated by thiol oxidation [29], increasing numbers of reports have recently shown that covalent modification of cysteines by disulfide formation can activate proteins in mammalian cells [30][31][32] and that disulfides are rapidly formed on cell surfaces in response to changes in the cellular redox state [28]. In agreement with these novel concepts, our finding that oxidative modification of caspase-9 can promote its activation has provided a previously undescribed perspective of how oxidative stress induces apoptosis; in addition to the Figure 5 Cys403 mutation blunted the sensitivity of caspase-9 to H 2 O 2 -induced auto-cleavage and decreased the formation of disulfide-dependent complex and apoptosomes.…”

Section: Discussionmentioning

confidence: 99%

Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1

et al. 2009

View full text Add to dashboard Cite

Intracellular reactive oxygen species (ROS) are known to regulate apoptosis. Activation of caspase-9, the initial caspase in the mitochondrial apoptotic cascade, is closely associated with ROS, but it is unclear whether ROS regulate caspase-9 via direct oxidative modification. The present study aims to elucidate the molecular mechanisms by which ROS mediate caspase-9 activation. Our results show that the cellular oxidative state facilitates caspase-9 activation. Hydrogen peroxide treatment causes the activation of caspase-9 and apoptosis, and promotes an interaction between caspase-9 and apoptotic protease-activating factor 1 (Apaf-1) via disulfide formation. In addition, in an in vitro mitochondria-free system, the thiol-oxidant diamide promotes auto-cleavage of caspase-9 and the caspase-9/ Apaf-1 interaction by facilitating the formation of disulfide-linked complexes. Finally, a point mutation at C403 of caspase-9 impairs both H 2 O 2 -promoted caspase-9 activation and interaction with Apaf-1 through the abolition of disulfide formation. The association between cytochrome c and the C403S mutant is significantly weaker than that between cytochrome c and wild-type caspase-9, indicating that oxidative modification of caspase-9 contributes to apoptosome formation under oxidative stress. Taken together, oxidative modification of caspase-9 by ROS can mediate its interaction with Apaf-1, and can thus promote its auto-cleavage and activation. This mechanism may facilitate apoptosome formation and caspase-9 activation under oxidative stress.

show abstract

“…A method to label disulfides in cells is described in a recent report [9]. The protocol uses iodoacetamide to block free thiols, DTT to reduce disulfides and iodoacetamide-conjugated fluorescein as a probe.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, proteomic methods to identify disulfides in proteins have been established [6][7][8]. However, means to image exact loci of thiol oxidation in cells and tissues are quite limited [9]. Imaging techniques would be particularly useful, since the redox environment differs between cell types and even subcellularly.…”

mentioning

confidence: 99%

“…In fact, because the formation of new disulfides will deplete only a small fraction of the free thiols, the difference in signal will be very small if free thiols are labeled. In contrast, formation of new disulfides will substantially increase the population of disulfides; therefore, labeling of disulfides provides a far more sensitive approach.A method to label disulfides in cells is described in a recent report [9]. The protocol uses iodoacetamide to block free thiols, DTT to reduce disulfides and iodoacetamide-conjugated fluorescein as a probe.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A FRET-based method to study protein thiol oxidation in histological preparations

Mastroberardino

Orr

et al. 2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Cysteine residues in proteins have important biological roles. For example, disulfides bonds are important structural elements; additionally, reversible oxidation of thiols to disulfides functions as a molecular switch and constitutes an early response to oxidative damage Because organs are heterogeneous structures composed of diverse cell types, there is a compelling need for a histological approach to investigate thiol oxidation in situ in order to address the role of specific cell types in oxidative imbalance. Here we describe a fluorescence technique -which can be used in association with standard immunological staining procedures -to detect variations in disulfides in histological preparations. Moreover, by monitoring the fluorescence resonance energy transfer (FRET) between a labeled specific primary antibody and the thiol probe described here, this method can detect thiol oxidation in candidate proteins of interest. When applied to an animal model of Parkinson's disease, our technique demonstrated that thiol oxidation occurs selectively in the dopaminergic neurons of the substantia nigra, the same neurons that are lost selectively in the disease. In summary, this technique provides a new, powerful tool to provide further understanding of oxidative imbalance, a phenomenon common to many diseases. Keywords fluorescence microscopy; FRET; oxidative stress; cysteine; thiols; disulfides; Parkinson's disease Thiols are the functional groups in the side chain of the amino acid, cysteine. Depending upon the oxido-reductive (redox) status of the surrounding environment, thiols exist either in the reduced form of free thiols (-SH) or oxidized to disulfides (-S-S-). Disulfides are well known to play an important structural role, contributing to the maintenance of the proper folding in proteins. More recently it was found that the formation of disulfides in proteins also exerts critical regulatory functions: vital mechanisms such as protein import, regulation of signal transduction cascades, regulation of the activity of transcription factors and proper function of the mitochondrial electron transport system rely on disulfide oxidation or reduction [1][2][3][4]. Moreover, the formation of disulfides represents an early, reversible response to oxidative *Corresponding author: mastroberardinopg@upmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Increasing interest in the study of thiols has led to the development of a variety of technical approaches to detect thiols and disulfides. In particular, several spectrophotometry-based protocols were developed to measure t...

show abstract

Regulation of the protein disulfide proteome by mitochondria in mammalian cells

Cited by 119 publications

References 27 publications

ERManI (Endoplasmic Reticulum Class I α-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway

ERManI (Endoplasmic Reticulum Class I α-Mannosidase) Is Required for HIV-1 Envelope Glycoprotein Degradation via Endoplasmic Reticulum-associated Protein Degradation Pathway

Oxidative modification of caspase-9 facilitates its activation via disulfide-mediated interaction with Apaf-1

A FRET-based method to study protein thiol oxidation in histological preparations

Contact Info

Product

Resources

About