Non-cytotoxic copper overload boosts mitochondrial energy metabolism to modulate cell proliferation and differentiation in the human erythroleukemic cell line K562

Ruíz, Lina; Jensen, Erik L.; Rossel, Yancing; Puas, German I.; González-Ibáñez, Alvaro M.; Bustos, Rodrigo I.; Ferrick, David A.; Elorza, Álvaro A.

doi:10.1016/j.mito.2016.04.005

Cited by 45 publications

(39 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Data were analyzed by two-tailed unpaired or paired Student's t -test, as appropriate, (when comparing two groups); or one- or two-way ANOVA with Tukey post hoc tests, as appropriate, (when comparing more than two groups). Frequency distributions were analyzed performing contingency tables and Chi-square tests [58]. P < 0.05 was considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells

Martínez

Tarallo

Martínez-Palma

et al. 2019

Biochemical Journal

View full text Add to dashboard Cite

Cellular senescence is an endpoint of chemotherapy, and targeted therapies in melanoma and the senescence-associated secretory phenotype (SASP) can affect tumor growth and microenvironment, influencing treatment outcomes. Metabolic interventions can modulate the SASP, and an enhanced mitochondrial energy metabolism supports resistance to therapy in melanoma cells. Herein, we assessed the mitochondrial function of therapy-induced senescent melanoma cells obtained after exposing the cells to temozolomide (TMZ), a methylating chemotherapeutic agent. Senescence induction in melanoma was accompanied by a substantial increase in mitochondrial basal, ATP-linked, and maximum respiration rates and in coupling efficiency, spare respiratory capacity, and respiratory control ratio. Further examinations revealed an increase in mitochondrial mass and length. Alterations in mitochondrial function and morphology were confirmed in isolated senescent cells, obtained by cell-size sorting. An increase in mitofusin 1 and 2 (MFN1 and 2) expression and levels was observed in senescent cells, pointing to alterations in mitochondrial fusion. Silencing mitofusin expression with short hairpin RNA (shRNA) prevented the increase in mitochondrial length, oxygen consumption rate and secretion of interleukin 6 (IL-6), a component of the SASP, in melanoma senescent cells. Our results represent the first in-depth study of mitochondrial function in therapy-induced senescence in melanoma. They indicate that senescence increases mitochondrial mass, length and energy metabolism; and highlight mitochondria as potential pharmacological targets to modulate senescence and the SASP.

show abstract

Section: Methodsmentioning

confidence: 99%

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells

Martínez

Tarallo

Martínez-Palma

et al. 2019

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Total protein oxidation was measured with the Oxyblot Detection Kit (Millipore) according to the manufacturer’s instructions. This measurement is based on the detection of carbonyl groups that are introduced into protein side chains when proteins are exposed to oxidative stress [37]. Briefly, total protein levels were quantified using the Bradford assay and using bovine serum albumin as a standard.…”

Section: Methodsmentioning

confidence: 99%

Alterations of Mitochondrial Biology in the Oral Mucosa of Chilean Children with Autism Spectrum Disorder (ASD)

Carrasco

Salazar

Tiznado

et al. 2019

Cells

View full text Add to dashboard Cite

Autistic Spectrum Disorder (ASD) is characterized by the impairment of socio-communicative skills and the presence of restricted and stereotyped behavior patterns. Recent researches have revealed the influence of mitochondrial physiology on the development of ASD. Several research groups have identified defects in respiratory complexes, coenzyme-Q10 deficiency, increased oxidative damage, decreased of superoxide dismutase (SOD2). A study on the influence of mitochondrial physiology on the development of ASD can provide new alternatives and challenges. That is why we set ourselves the general objective to initiate studies of mitochondrial physiology in Chilean children with ASD. A sample of oral mucosa was collected in a group of 12 children diagnosed with ASD and 12 children without ASD. In children with ASD, we found a significant increase in mitochondrial DNA levels. Likewise, in these children, an increase in the protein oxidation was observed. Finally, a downward trend in the expression of the HIGD2A and SOD2 genes was observed, while DRP1, FIS1, MFN1, MFN2, and OPA1 gene expression show an upward trend. The increment of mitochondrial DNA, high oxidative stress, and high expression of the MFN2 gene could help as a scanner of the mitochondrial function in children with ASD.

show abstract

“…Copper (Cu) is an essential micronutrient required for many biological processes in vivo , such as respiration, iron transport, oxidative stress protection, peptide hormone production, pigmentation, blood clotting, and normal cell growth and development 1–4 . Although Cu is not always abundant in the in vivo environment, cells have evolved a complex system of Cu transporters and chaperones that accumulate Cu 3 .…”

Section: Introductionmentioning

confidence: 99%

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

Jiang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

At present, 64Cu(II) labeled tracers including 64CuCl2 have been widely applied in the research of molecular imaging and therapy. Human copper transporter 1 (hCTR1) is the major high affinity copper influx transporter in mammalian cells, and specially responsible for the transportation of Cu(I) not Cu(II). Thus, we investigated the feasible application of 64Cu(I) for PET imaging. 64Cu(II) was reduced to 64Cu(I) with the existence of sodium L-ascorbate, DL-Dithiothreitol or cysteine. Cell uptake and efflux assay was investigated using B16F10 and A375 cell lines, respectively. Small animal PET and biodistribution studies were performed in both B16F10 and A375 tumor-bearing mice. Compared with 64Cu(II), 64Cu(I) exhibited higher cellular uptake by melanoma, which testified CTR1 specially influx of Cu(I). However, due to oxidation reaction in vivo, no significant difference between 64Cu(I) and 64Cu(II) was observed through PET images and biodistribution. Additionally, radiation absorbed doses for major tissues of human were calculated based on the mouse biodistribution. Radiodosimetry calculations for 64/67Cu(I) and 64/67Cu(II) were similar, which suggested that although melanoma were with high radiation absorbed doses, high radioactivity accumulation by liver and kidney should be noticed for the further application. Thus, 64Cu(I) should be further studied to evaluate it as a PET imaging radiotracer.

show abstract

Non-cytotoxic copper overload boosts mitochondrial energy metabolism to modulate cell proliferation and differentiation in the human erythroleukemic cell line K562

Cited by 45 publications

References 79 publications

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells

Mitofusins modulate the increase in mitochondrial length, bioenergetics and secretory phenotype in therapy-induced senescent melanoma cells

Alterations of Mitochondrial Biology in the Oral Mucosa of Chilean Children with Autism Spectrum Disorder (ASD)

Pilot Study of 64Cu(I) for PET Imaging of Melanoma

Contact Info

Product

Resources

About