Chaperone-like activity of macrophage migration inhibitory factor

Cherepkova, O. A.; Lyutova, Elena M.; Eronina, Tatiana B.; Gurvits, B. Ya.

doi:10.1016/j.biocel.2005.07.001

Cited by 37 publications

(37 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytokine activity of MIF is achieved by posttranslational sequestration of the cytoplasmic MIF into vesicles, followed by its release, through an as-yet unidentified mechanism, in response to a variety of signals (29). Intracellularly, MIF was previously shown to act as a chaperone protein (30) and as a thiol-protein oxidoreductase (31).…”

Section: Discussionmentioning

confidence: 99%

Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS

Leyton-Jaimes

Benaim

Abu-Hamad

et al. 2016

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

View full text Add to dashboard Cite

Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by the loss of upper and lower motor neurons in the brain and spinal cord. It has been suggested that the toxicity of mutant SOD1 results from its misfolding and accumulation on the cytoplasmic faces of intracellular organelles, including the mitochondria and endoplasmic reticulum (ER) of ALS-affected tissues. Recently, macrophage migration inhibitory factor (MIF) was shown to directly inhibit the accumulation of misfolded SOD1 and its binding to intracellular membranes, but the role of endogenous MIF in modulating SOD1 misfolding in vivo remains unknown. To elucidate this role, we bred MIF-deficient mice with SOD1 G85R mice, which express a dismutase-inactive mutant of SOD1 and are considered a model of familial ALS. We found that the accumulation of misfolded SOD1, its association with mitochondrial and ER membranes, and the levels of sedimentable insoluble SOD1 aggregates were significantly higher in the spinal cords of SOD1 G85R -MIF −/− mice than in their SOD1 G85R -MIF +/+ littermates. Moreover, increasing MIF expression in neuronal cultures inhibited the accumulation of misfolded SOD1 and rescued from mutant SOD1-induced cell death. In contrast, the complete elimination of endogenous MIF accelerated disease onset and late disease progression and shortened the lifespan of the SOD1 G85R mutant mice. These findings indicate that MIF plays a significant role in the folding and misfolding of SOD1 in vivo, and they have implications for the potential therapeutic role of upregulating MIF within the nervous system to modulate the selective accumulation of misfolded SOD1.ALS | mutant SOD1 mouse | mutant SOD1 | misfolded SOD1 | MIF

show abstract

Section: Discussionmentioning

confidence: 99%

Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS

Leyton-Jaimes

Benaim

Abu-Hamad

et al. 2016

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

View full text Add to dashboard Cite

show abstract

“…Here we purify a cytosolic activity whose action inhibits mutant SOD1 misfolding onto mitochondria and ER. We identify this factor to be macrophage migration inhibitory factor (MIF), a multifunctional protein whose activities include an ATP-independent protein folding chaperone (Cherepkova et al, 2006). We propose that a low MIF level within motor neurons is one component of their selective vulnerability to ubiquitously expressed mutations in SOD1.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Migration Inhibitory Factor as a Chaperone Inhibiting Accumulation of Misfolded SOD1

Israelson

Ditsworth

Sun

et al. 2015

Neuron

104

126

View full text Add to dashboard Cite

Summary Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by loss of motor neurons and accompanied by accumulation of misfolded SOD1 onto the cytoplasmic faces of intracellular organelles, including mitochondria and endoplasmic reticulum (ER). Using inhibition of misfolded SOD1 deposition onto mitochondria as an assay, a chaperone activity abundant in non-neuronal tissues is now purified and identified to be the multifunctional macrophage migration inhibitory factor (MIF), whose activities include an ATP-independent protein folding chaperone. Purified MIF is shown to directly inhibit mutant SOD1 misfolding. Elevating MIF in neuronal cells suppresses accumulation of misfolded SOD1 and its association with mitochondria and ER and extends survival of mutant SOD1-expressing motor neurons. Accumulated MIF protein is identified to be low in motor neurons, implicating correspondingly low chaperone activity as a component of vulnerability to mutant SOD1 misfolding and supporting therapies to enhance intracellular MIF chaperone activity.

show abstract

“…Currently, it is widely accepted that MIF represents a molecule with a plethora of functions (reviewed in [7][8][9]). MIF namely possesses the properties of a cytokine [10], enzyme [11], endocrine molecule [12] and a chaperon-like protein [13]. It is produced by various cell types including immune cells such as T and B lymphocytes [14,15], monocytes and macrophages [16], blood dendritic cells [17], eosinophils [18], neutrophils [19], mast cells [20] and non-immune cells such as epithelial cells of many organs (reviewed in [9]), pancreatic β cells [21], anterior pituitary cells [10], cardiac myocytes [22], and parenchymal cells within the liver, brain, or kidneys [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

Neutralization of macrophage migration inhibitory factor—novel approach for the treatment of immunoinflammatory disorders

Cvetković¹,

Stošić‐Grujičić²

2006

International Immunopharmacology

View full text Add to dashboard Cite

Chaperone-like activity of macrophage migration inhibitory factor

Cited by 37 publications

References 51 publications

Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS

Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS

Macrophage Migration Inhibitory Factor as a Chaperone Inhibiting Accumulation of Misfolded SOD1

Neutralization of macrophage migration inhibitory factor—novel approach for the treatment of immunoinflammatory disorders

Contact Info

Product

Resources

About