Impaired Manganese Metabolism Causes Mitotic Misregulation

García‐Rodríguez, Néstor; Loza, María del Carmen Díaz de la; Andreson, Bethany L.; Monje-Casas, Fernando; Rothstein, Rodney; Wellinger, Ralf Erik

doi:10.1074/jbc.m112.358309

Cited by 14 publications

(14 citation statements)

References 69 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The contribution of defective Mn 2ϩ transport on Hailey-Hailey disease progression is still under debate. However, increasing evidence points to the possibility that impaired manganese homeostasis triggers keratinocyte differentiation (6) and causes genetic instability (2).…”

Section: Discussionmentioning

confidence: 99%

“…2ϩ Toxicity-In a previous work we found that an excess of cytosolic Mn 2ϩ alters mRNA transcription regulation and challenges genome stability (2). An example is the transcriptional 42-fold down-regulation of the low-affinity plasma membrane Mn 2ϩ transporter PHO84 (YML123C).…”

Section: Cacl 2 Counteracts Mnmentioning

confidence: 99%

“…This redox active metal is a key cofactor for a wide range of enzymes located in every cellular compartment (1). However, at high concentrations Mn 2ϩ is toxic and promotes DNA damage coupled to replication defects in yeast (2). In humans, overexposure to Mn 2ϩ results in a neurological syndrome called manganism, whose symptoms resemble those of Parkinson disease (3).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Manganese Redistribution by Calcium-stimulated Vesicle Trafficking Bypasses the Need for P-type ATPase Function

García‐Rodríguez

Manzano-López

Muñoz-Bravo

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Background: Yeast is a model system for the study of mechanisms governing eukaryotic Golgi-Mn 2ϩ homeostasis. Results: We provide evidence that calcium stimulates ER and late endosome/trans-to cis-Golgi manganese delivery and bypasses the need for Pmr1. Conclusion: Vesicle trafficking promotes organelle-specific ion interchange and cytoplasmic metal detoxification. Significance: Our findings open new perspectives on chemical modifiers of Hailey-Hailey disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Cacl 2 Counteracts Mnmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Manganese Redistribution by Calcium-stimulated Vesicle Trafficking Bypasses the Need for P-type ATPase Function

García‐Rodríguez

Manzano-López

Muñoz-Bravo

et al. 2015

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mn excess can also be detrimental to organisms. Mn toxicity leads to a predisposition to genomic instability (García-Rodríguez et al, 2012) and causes a neurological syndrome in human called manganism, with symptoms resembling those of Parkinson disease (Roth, 2006). In plants, Mn toxicity is widespread in acidic soils, where it becomes more available and provokes quite diverse symptoms often characterized by brown speckles containing oxidized Mn on mature leaves and/or interveinal chlorosis and necrosis (Marschner et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Intracellular Distribution of Manganese by the Trans-Golgi Network Transporter NRAMP2 Is Critical for Photosynthesis and Cellular Redox Homeostasis

et al. 2017

View full text Add to dashboard Cite

Plants require trace levels of manganese (Mn) for survival, as it is an essential cofactor in oxygen metabolism, especially O production via photosynthesis and the disposal of superoxide radicals. These processes occur in specialized organelles, requiring membrane-bound intracellular transporters to partition Mn between cell compartments. We identified an member of the NRAMP family of divalent metal transporters, NRAMP2, which functions in the intracellular distribution of Mn. Two knockdown alleles of showed decreased activity of photosystem II and increased oxidative stress under Mn-deficient conditions, yet total Mn content remained unchanged. At the subcellular level, these phenotypes were associated with a loss of Mn content in vacuoles and chloroplasts. NRAMP2 was able to rescue the mitochondrial yeast mutant In plants, NRAMP2 is a resident protein of the-Golgi network. NRAMP2 may act indirectly on downstream organelles by building up a cytosolic pool that is used to feed target compartments. Moreover, not only does the mutant accumulate superoxide ions, but NRAMP2 can functionally replace cytosolic superoxide dismutase in yeast, indicating that the pool of Mn displaced by NRAMP2 is required for the detoxification of reactive oxygen species.

show abstract

“…Misregulation of Mn2 + homeostasis impairs genome replication and cell cycle progression. Furthermore, genome instability and endomitosis can be triggered by alterations in cytosolic or Golgi Mn2 + levels (García-Rodríguez et al 2012). Homeostasis of Mn tissue content is controlled by uptake, distribution and elimination mechanisms (Abrams et al 1976).…”

Section: Introductionmentioning

confidence: 99%

Effect of Different Manganese Concentrations during in vitro Maturation of Bovine Oocytes on DNA Integrity of Cumulus Cells and Subsequent Embryo Development

Anchordoquy

Sirini

Mattioli

et al. 2013

Reprod Domestic Animals

View full text Add to dashboard Cite

Manganese (Mn) is a trace element present in forages and cereals, and its concentration depends on soil status. Manganese deficiency in cattle, goats and ewes not only impairs oestrous cycle but reduces calf birth weight. The achievement of the first oestrus is delayed, and more attempts are necessary to obtain a successful conception. This study was conducted to investigate the effect of the availability of supplemental Mn during IVM on DNA damage of cumulus cells and total glutathione (GSH) content in oocytes and cumulus cells. The effect of supplementary Mn during IVM on subsequent embryo development was also studied. The results reported here indicate (i) DNA damage in cumulus cells decreased with 0, 2, 5 and 6 ng/ml Mn supplementation during IVM (p < 0.05). (ii) Intracellular GSH-GSSG content increased (p < 0.01) with different Mn concentrations in oocytes and cumulus cells. Also, cumulus cell number per cumulus oocyte-complexes (COC) did not differ either before or after IVM. (iii) Addition of Mn to maturation medium resulted in similar cleavage rates (p > 0.05) at 0, 2, 5 and 6 ng/ml Mn. However, subsequent embryo development to blastocyst stage was significantly higher (p < 0.01) in oocytes matured with 5 and 6 ng/ml Mn. (iv) There was also an increase (p < 0.05) in mean cell number per blastocyst obtained from oocytes matured with 5 and 6 ng/ml respect to zero Mn (IVM alone) and 2 ng/ml Mn. This study provides evidence that optimal embryo development to the blastocyst stage was partially dependent on the presence of Mn during IVM. Moreover, the availability of Mn during oocyte maturation ensures 'normal' intracellular GSH content in COCs and protects DNA integrity of cumulus cells.

show abstract

Impaired Manganese Metabolism Causes Mitotic Misregulation

Cited by 14 publications

References 69 publications

Manganese Redistribution by Calcium-stimulated Vesicle Trafficking Bypasses the Need for P-type ATPase Function

Manganese Redistribution by Calcium-stimulated Vesicle Trafficking Bypasses the Need for P-type ATPase Function

Intracellular Distribution of Manganese by the Trans-Golgi Network Transporter NRAMP2 Is Critical for Photosynthesis and Cellular Redox Homeostasis

Effect of Different Manganese Concentrations during in vitro Maturation of Bovine Oocytes on DNA Integrity of Cumulus Cells and Subsequent Embryo Development

Contact Info

Product

Resources

About