In yeast redistribution of Sod1 to the mitochondrial intermembrane space provides protection against respiration derived oxidative stress

Klöppel, Christine; Michels, Christine; Zimmer, Julia; Herrmann, Johannes M.; Riemer, Jan

doi:10.1016/j.bbrc.2010.10.129

Cited by 35 publications

(30 citation statements)

References 26 publications

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“…This has been explained by excessive dismutase activity of mutant SOD1 (Goldsteins et al 2008;Wiedau-Pazos et al 1996), increased levels of ROS produced by mitochondria following inhibition of complex I (Kruman et al 1999;Mattiazzi et al 2002;Murphy 2009;Zimmerman et al 2007), or increased NADPH oxidase (NOX) activity through mutant SOD1 interacting with Rac1, a NOX regulator (reviewed in Boillee and Cleveland 2008). It should be noted, however, that recent data indicate that overexpression of mutant SOD1 G93A in yeast cells actually provided increased protection against respiration-derived ROS (Kloppel et al 2010).…”

Section: Mitochondrial Morphological Abnormalities and Dysfunctions Imentioning

confidence: 99%

Mitochondrial dysfunction in familial amyotrophic lateral sclerosis

Faes¹,

Callewaert²

2011

J Bioenerg Biomembr

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A growing body of evidence suggests that mitochondrial dysfunctions play a crucial role in the pathogenesis of various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting both upper and lower motor neurons. Although ALS is predominantly a sporadic disease, approximately 10% of cases are familial. The most frequent familial form is caused by mutations in the gene encoding Cu/Zn superoxide dismutase 1 (SOD1). A dominant toxic gain of function of mutant SOD1 has been considered as the cause of the disease and mitochondria are thought to be key players in the pathogenesis. However, the exact nature of the link between mutant SOD1 and mitochondrial dysfunctions remains to be established. Here, we briefly review the evidence for mitochondrial dysfunctions in familial ALS and discuss a possible link between mutant SOD1 and mitochondrial dysfunction.

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Section: Mitochondrial Morphological Abnormalities and Dysfunctions Imentioning

confidence: 99%

Mitochondrial dysfunction in familial amyotrophic lateral sclerosis

Faes¹,

Callewaert²

2011

J Bioenerg Biomembr

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“…Samples were centrifuged at 1,000 g for 5 min and supernatants were analysed by SDS-PAGE. Isolation of the mitochondria from S. cerevisiae was performed as described 7 . In short, after cell walls were broken by Zymolyase treatment, cells were homogenized on ice with a Potter-Elvehjem homogenizer in a buffer consisting of 0.6 M sorbitol, 1 mM EDTA and 10 mM Tris-HCl (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

“…The subcellular localization of SOD activity may not only be important for the removal of O 2 À but could also contribute to the site-specific generation of the signalling molecule H 2 O 2 . As O 2 À is mainly generated by the respiratory chain, the localization of SOD1 to the mitochondrial IMS is especially interesting, because SOD1 might mediate a signalling pathway that communicates activity states of the respiratory chain and oxidative stress to the cytosol 7,8 .…”

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confidence: 99%

Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria

et al. 2013

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Oxidative stress is counteracted by various cellular systems, including copper-zinc superoxide dismutase 1 (SOD1) and its activating chaperone, that is, the copper chaperone for SOD1 (CCS1). Both enzymes are structurally related, and both localize to the cytosol and the mitochondrial intermembrane space where they specifically counteract mitochondria-derived superoxide. The mechanism by which human CCS1 is transported into mitochondria is largely unclear. Here we show that CCS1 import depends on the presence of mature CCS1 in the mitochondria. During import, a disulphide bond is formed in CCS1 in a CCS1-dependent reaction. We demonstrate that oxidation and import depend on the presence of cysteine residues at positions 227 and 141/144 in CCS1. Notably, CCS1 import parallels SOD1 import that also depends on CCS1. Our observations suggest that CCS1 serves as a specialized import receptor in mitochondria that facilitates the import and folding of SOD1 and CCS1, thereby extending the substrate spectrum of oxidation-dependent protein import in the mitochondrial intermembrane space.

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“…The insertion of this disulfide bond and of the copper ion is facilitated by Ccs1 (83)(84)(85). The majorities of both proteins are present in the cytosol; however, small amounts are also found in the IMS of mitochondria (84,86,87). It was proposed that Ccs1 mediates the import of Sod1 into the IMS because up-regulation of Ccs1 in the IMS results in an increase of Sod1 in this compartment (84).…”

Section: Substrates Of Mitochondrial Disulfide Relaymentioning

confidence: 99%

Mitochondrial Disulfide Relay: Redox-regulated Protein Import into the Intermembrane Space

Herrmann

Riemer

2012

Journal of Biological Chemistry

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107

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99% of all mitochondrial proteins are synthesized in the cytosol, from where they are imported into mitochondria. In contrast to matrix proteins, many proteins of the intermembrane space (IMS) lack presequences and are imported in an oxidation-driven reaction by the mitochondrial disulfide relay. Incoming polypeptides are recognized and oxidized by the IMSlocated receptor Mia40. Reoxidation of Mia40 is facilitated by the sulfhydryl oxidase Erv1 and the respiratory chain. Although structurally unrelated, the mitochondrial disulfide relay functionally resembles the Dsb (disufide bond) system of the bacterial periplasm, the compartment from which the IMS was derived 2 billion years ago.Mitochondria consist of two aqueous compartments, the matrix and the intermembrane space (IMS).2 The mitochondrial genome codes only for roughly a dozen different proteins, and the vast majority of mitochondrial proteins are nuclear encoded. Even simple organisms such as bakers' yeast contain several hundred matrix proteins. Matrix proteins are synthesized in the cytosol as precursors with N-terminal presequences (also referred to as matrix-targeting signals), which are processed following translocation. The import of matrix-destined preproteins is mediated by translocases in the outer membrane (TOM complex) and inner membrane (TIM23 complex) in an ATP-and membrane potential-dependent process (for review, see Refs. 1-3). Proteomic studies suggest that positively charged presequences are consistently found on all matrix proteins, although in some cases they are not proteolytically removed (4, 5).So far, ϳ50 different proteins were identified in the IMS of yeast mitochondria, and the list of IMS proteins is rapidly growing (6). The functions of these proteins are diverse. In addition to components involved in mitochondrial respiration, the IMS contains many proteins that transport proteins, metabolites, lipids, or metal ions between both mitochondrial membranes. In addition, several pro-apoptotic components are stored in the IMS and released when the cell death program is triggered (7).Some IMS proteins are synthesized in the cytosol as preproteins carrying bipartite presequences that consist of a matrixtargeting signal followed by a hydrophobic sorting region. The latter serves as a stop-transfer sequence that is inserted into the inner membrane during protein import and removed by IMSlocated proteases (8). Proteins with bipartite presequences embark on the general matrix-directed protein-targeting pathway, from which they are redirected into the IMS. However, many IMS proteins lack N-terminal targeting signals and are sorted into the IMS on a unique import route that differs in many respects from the matrix-targeting pathway. Import of many of these proteins relies on the mitochondrial disulfide relay, which is introduced below. Mitochondrial Disulfide Relay: Mia40 and Erv1The IMS proteins Mia40 (mitochondrial IMS import and assembly pathway 40 kDa) and Erv1 (essential for respiratory growth and viability 1) represent the central com...

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In yeast redistribution of Sod1 to the mitochondrial intermembrane space provides protection against respiration derived oxidative stress

Cited by 35 publications

References 26 publications

Mitochondrial dysfunction in familial amyotrophic lateral sclerosis

Mitochondrial dysfunction in familial amyotrophic lateral sclerosis

Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria

Mitochondrial Disulfide Relay: Redox-regulated Protein Import into the Intermembrane Space

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