SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration

Reddi, Amit R.; Culotta, Valeria C.

doi:10.1016/j.cell.2012.11.046

Cited by 186 publications

(218 citation statements)

References 67 publications

(68 reference statements)

Supporting

Mentioning

203

Contrasting

Order By: Relevance

“…The numbers for baboon (20), macaque (18), and gibbon (18) are also consistent with this approximate rate.…”

Section: Resultssupporting

confidence: 70%

See 1 more Smart Citation

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

Dasmeh

Kepp

2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

“…The numbers for baboon (20), macaque (18), and gibbon (18) are also consistent with this approximate rate.…”

Section: Resultssupporting

confidence: 70%

“…SOD1 is a central repressor of cellular respiration by integrating oxygen, superoxide, and glucose signals [20]. It is a dimeric protein with a Cu and a Zn metal ion essential for its catalytic function [19]; its structure is dominated by the β-sheet Greek-Key fold of each dimer, which evolved from gene duplication events [21].…”

Section: Introductionmentioning

confidence: 99%

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

Dasmeh

Kepp

2017

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

“…Interaction of WT SOD1 with two casein kinases has been recently reported in the context of a signaling cascade that controls cellular respiration (41). There is also a report that WT SOD1 can bind directly to Rac1 and affect its activity (42).…”

Section: Discussionmentioning

confidence: 95%

Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm

Song

Nagy

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mutant human Cu/Zn superoxide dismutase 1 (SOD1) is associated with motor neuron toxicity and death in an inherited form of amyotrophic lateral sclerosis (ALS; Lou Gehrig disease). One aspect of toxicity in motor neurons involves diminished fast axonal transport, observed both in transgenic mice and, more recently, in axoplasm isolated from squid giant axons. The latter effect appears to be directly mediated by misfolded SOD1, whose addition activates phosphorylation of p38 MAPK and phosphorylation of kinesin. Here, we observe that several different oligomeric states of a fusion protein, comprising ALS-associated human G85R SOD1 joined with yellow fluorescent protein (G85R SOD1YFP), which produces ALS in transgenic mice, inhibited anterograde transport when added to squid axoplasm. Inhibition was blocked both by an apoptosis signal-regulating kinase 1 (ASK1; MAPKKK) inhibitor and by a p38 inhibitor, indicating the transport defect is mediated through the MAPK cascade. In further incubations, we observed that addition of the mammalian molecular chaperone Hsc70, abundantly associated with G85R SOD1YFP in spinal cord of transgenic mice, exerted partial correction of the transport defect, associated with diminished phosphorylation of p38. Most striking, the addition of the molecular chaperone Hsp110, in a concentration substoichiometric to the mutant SOD1 protein, completely rescued both the transport defect and the phosphorylation of p38. Hsp110 has been demonstrated to act as a nucleotide exchange factor for Hsc70 and, more recently, to be able to cooperate with it to mediate protein disaggregation. We speculate that it can cooperate with endogenous squid Hsp(c)70 to mediate binding and/or disaggregation of mutant SOD1 protein, abrogating toxicity.

show abstract

“…The genes for mKATE2 and CG6 used to construct HS1 were purchased from GENESCRIPT and codon-optimized for expression in E. coli and S. cerevisiae or humans. Standard published methods for protein expression and purification (18), heme binding studies (20,27), fluorimetry, UV/visible spectroscopy, microscopy, flow cytometry, immunoblotting (41), catalase activity (34), oxygen consumption (41), total heme analysis (42), and cell growth are outlined in SI Appendix, SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Heme dynamics and trafficking factors revealed by genetically encoded fluorescent heme sensors

Hanna

Harvey

Martinez-Guzman

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

160

405

View full text Add to dashboard Cite

Heme is an essential cofactor and signaling molecule. Heme acquisition by proteins and heme signaling are ultimately reliant on the ability to mobilize labile heme (LH). However, the properties of LH pools, including concentration, oxidation state, distribution, speciation, and dynamics, are poorly understood. Herein, we elucidate the nature and dynamics of LH using genetically encoded ratiometric fluorescent heme sensors in the unicellular eukaryote Saccharomyces cerevisiae. We find that the subcellular distribution of LH is heterogeneous; the cytosol maintains LH at ∼20–40 nM, whereas the mitochondria and nucleus maintain it at concentrations below 2.5 nM. Further, we find that the signaling molecule nitric oxide can initiate the rapid mobilization of heme in the cytosol and nucleus from certain thiol-containing factors. We also find that the glycolytic enzyme glyceraldehyde phosphate dehydrogenase constitutes a major cellular heme buffer, and is responsible for maintaining the activity of the heme-dependent nuclear transcription factor heme activator protein (Hap1p). Altogether, we demonstrate that the heme sensors can be used to reveal fundamental aspects of heme trafficking and dynamics and can be used across multiple organisms, including Escherichia coli, yeast, and human cell lines.

show abstract

SOD1 Integrates Signals from Oxygen and Glucose to Repress Respiration

Cited by 186 publications

References 67 publications

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

Molecular chaperone Hsp110 rescues a vesicle transport defect produced by an ALS-associated mutant SOD1 protein in squid axoplasm

Heme dynamics and trafficking factors revealed by genetically encoded fluorescent heme sensors

Contact Info

Product

Resources

About