Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics

Lina María Ruiz, Erik L. Jensen, Rodrigo I. Bustos, Graciela Argüelloa, Ricardo Gutierrez-Garcia, Mauricio González, Claudia Hernández, Rodolfo Paredes, Felipe Simon, Claudia Riedel, David Ferrick, Alvaro A. Elorza

Resultado de la investigación: Article

10 Citas (Scopus)

Resumen

Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation.

Idioma originalEnglish
Páginas (desde-hasta)607-619
Número de páginas13
PublicaciónJournal of Cellular Physiology
Volumen229
N.º5
DOI
EstadoPublished - 2014

Huella dactilar

Mitochondria
Energy Metabolism
Copper
Mitochondrial Dynamics
Metabolism
Liver
Animals
Adenosine Triphosphate
Oligomycins
Cucurbita
Liver Mitochondrion
Mitochondrial Membrane Potential
Erythropoiesis
Mitochondrial Proteins
Respiratory Rate
Intraperitoneal Injections
Adenosine Diphosphate
Anemia
Respiration
Necrosis

ASJC Scopus subject areas

  • Medicine(all)
  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Ruiz, Lina María ; Jensen, Erik L. ; Bustos, Rodrigo I. ; Argüelloa, Graciela ; Gutierrez-Garcia, Ricardo ; González, Mauricio ; Hernández, Claudia ; Paredes, Rodolfo ; Simon, Felipe ; Riedel, Claudia ; Ferrick, David ; Elorza, Alvaro A. / Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics. En: Journal of Cellular Physiology. 2014 ; Vol. 229, N.º 5. pp. 607-619.
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title = "Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics",
abstract = "Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the {"}butternut squash{"} mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation.",
author = "Ruiz, {Lina Mar{\'i}a} and Jensen, {Erik L.} and Bustos, {Rodrigo I.} and Graciela Arg{\"u}elloa and Ricardo Gutierrez-Garcia and Mauricio Gonz{\'a}lez and Claudia Hern{\'a}ndez and Rodolfo Paredes and Felipe Simon and Claudia Riedel and David Ferrick and Elorza, {Alvaro A.}",
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Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics. / Ruiz, Lina María; Jensen, Erik L.; Bustos, Rodrigo I.; Argüelloa, Graciela; Gutierrez-Garcia, Ricardo; González, Mauricio; Hernández, Claudia; Paredes, Rodolfo; Simon, Felipe; Riedel, Claudia; Ferrick, David; Elorza, Alvaro A.

En: Journal of Cellular Physiology, Vol. 229, N.º 5, 2014, p. 607-619.

Resultado de la investigación: Article

TY - JOUR

T1 - Adaptive responses of mitochondria to mild copper deprivation involve changes in morphology, OXPHOS remodeling and bioenergetics

AU - Ruiz, Lina María

AU - Jensen, Erik L.

AU - Bustos, Rodrigo I.

AU - Argüelloa, Graciela

AU - Gutierrez-Garcia, Ricardo

AU - González, Mauricio

AU - Hernández, Claudia

AU - Paredes, Rodolfo

AU - Simon, Felipe

AU - Riedel, Claudia

AU - Ferrick, David

AU - Elorza, Alvaro A.

PY - 2014

Y1 - 2014

N2 - Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation.

AB - Copper is an essential cofactor of complex IV of the electron transfer chain, and it is directly involved in the generation of mitochondrial membrane potential. Its deficiency induces the formation of ROS, large mitochondria and anemia. Thus, there is a connection between copper metabolism and bioenergetics, mitochondrial dynamics and erythropoiesis. Copper depletion might end in cellular apoptosis or necrosis. However, before entering into those irreversible processes, mitochondria may execute a series of adaptive responses. Mitochondrial adaptive responses (MAR) may involve multiple and diverse mechanisms for preserving cell life, such as mitochondrial dynamics, OXPHOS remodeling and bioenergetics output. In this study, a mild copper deficiency was produced in an animal model through intraperitoneal injections of bathocuproine disulfonate in order to study the MAR. Under these conditions, a new type of mitochondrial morphology was discovered in the liver. Termed the "butternut squash" mitochondria, it coexisted with normal and swollen mitochondria. Western blot analyses of mitochondrial dynamics proteins showed an up-regulation of MFN-2 and OPA1 fusion proteins. Furthermore, isolated liver mitochondria displayed OXPHOS remodeling through a decrease in supercomplex activity with a concomitant increase at an individual level of complexes I and IV, higher respiratory rates at complex I and II levels, higher oligomycin-insensitive respiration, and lower respiratory control ratio values when compared to the control group. As expected, total ATP and ATP/ADP values were not significantly different, since animal's health was not compromised. As a whole, these results describe a compensatory and adaptive response of metabolism and bioenergetics under copper deprivation.

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DO - 10.1002/jcp.24484

M3 - Article

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JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

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