Non-cytotoxic copper overload boosts mitochondrial energy metabolism to modulate cell proliferation and differentiation in the human erythroleukemic cell line K562.
Copper is integral to the mitochondrial respiratory complex IV and contributes to proliferation and differentiation, metabolic reprogramming and mitochondrial function. The K562 cell line was exposed to a non-cytotoxic copper overload to evaluate mitochondrial dynamics, function and cell fate. This induced higher rates of mitochondrial turnover given by an increase in mitochondrial fusion and fission events and in the autophagic flux. The appearance of smaller and condensed mitochondria was also observed. Bioenergetics activity included more respiratory complexes, higher oxygen consumption rate, superoxide production and ATP synthesis, with no decrease in membrane potential. Increased cell proliferation and inhibited differentiation also occurred. Non-cytotoxic copper levels can modify mitochondrial metabolism and cell fate, which could be used in cancer biology and regenerative medicine.
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile; Centro de Investigación Biomédica, Universidad Autónoma de Chile, 7500912 Santiago, Chile.
Lina M
LM
Ruiz
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile.
Erik L
EL
Jensen
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile.
Yancing
Y
Rossel
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile; Millennium Institute of Immunology and Immunotherapy, 8331150 Santiago, Chile.
German I
GI
Puas
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile; Millennium Institute of Immunology and Immunotherapy, 8331150 Santiago, Chile.
Alvaro M
AM
Gonzalez-Ibanez
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile.
Rodrigo I
RI
Bustos
Seahorse Bioscience, Billerica, MA 01862, USA.
David A
DA
Ferrick
Center for Biomedical Research, Faculty of Biological Sciences and Faculty of Medicine, Universidad Andres Bello, 8370146, Santiago, Chile; Millennium Institute of Immunology and Immunotherapy, 8331150 Santiago, Chile. Electronic address: alvaro.elorza@unab.cl.
Alvaro A
AA
Elorza
D002454:Cell Differentiation; D049109:Cell Proliferation; D003300:Copper / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D008928:Mitochondria / Q000187:drug effects*
D003300:Copper
Autophagy; Bioenergetics; Copper; Erythropoiesis; Mitochondria; Mitochondrial dynamics