Marín Buera, Lorena García Bartolomé, Alberto Morán Jiménez, María Josefa Arenas Barbero, Joaquín Hidalgo, Beatriz Martín, Miguel A. Ugalde Bilbao, Cristina Sánchez Pérez, Ricardo
Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency. [artículo] - Journal of proteomics, 2015 - 113:38-56.
Formato Vancouver:
Marín-Buera L, García-Bartolomé A, Morán M, López-Bernardo E, Cadenas S, Hidalgo B et al. Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency. J Proteomics. 2015 Jan 15;113:38-56.
PMID: 25239759
PMC4259860
Contiene 64 referencias
We have analyzed the cellular pathways and metabolic adaptations that take place in primary skin fibroblasts from patients with mutations in BCS1L, a major genetic cause of mitochondrial complex III enzyme deficiency. Mutant fibroblasts exhibited low oxygen consumption rates and intracellular ATP levels, indicating that the main altered molecular event probably is a limited respiration-coupled ATP production through the OXPHOS system. Two-dimensional DIGE and MALDI-TOF/TOF mass spectrometry analyses unambiguously identified 39 proteins whose expression was significantly altered in complex III-deficient fibroblasts. Extensive statistical and cluster analyses revealed a protein profile characteristic for the BCS1L mutant fibroblasts that included alterations in energy metabolism, cell signaling and gene expression regulation, cytoskeleton formation and maintenance, and intracellular stress responses. The physiological validation of the predicted functional adaptations of human cultured fibroblasts to complex III deficiency confirmed the up-regulation of glycolytic enzyme activities and the accumulation of branched-chain among other amino acids, suggesting the activation of anaerobic glycolysis and cellular catabolic states, in particular protein catabolism, together with autophagy as adaptive responses to mitochondrial respiratory chain dysfunction and ATP deficiency. Our data point to an overall metabolic and genetic reprogramming that could contribute to explain the clinical manifestations of complex III deficiency in patients.
Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency. [artículo] - Journal of proteomics, 2015 - 113:38-56.
Formato Vancouver:
Marín-Buera L, García-Bartolomé A, Morán M, López-Bernardo E, Cadenas S, Hidalgo B et al. Differential proteomic profiling unveils new molecular mechanisms associated with mitochondrial complex III deficiency. J Proteomics. 2015 Jan 15;113:38-56.
PMID: 25239759
PMC4259860
Contiene 64 referencias
We have analyzed the cellular pathways and metabolic adaptations that take place in primary skin fibroblasts from patients with mutations in BCS1L, a major genetic cause of mitochondrial complex III enzyme deficiency. Mutant fibroblasts exhibited low oxygen consumption rates and intracellular ATP levels, indicating that the main altered molecular event probably is a limited respiration-coupled ATP production through the OXPHOS system. Two-dimensional DIGE and MALDI-TOF/TOF mass spectrometry analyses unambiguously identified 39 proteins whose expression was significantly altered in complex III-deficient fibroblasts. Extensive statistical and cluster analyses revealed a protein profile characteristic for the BCS1L mutant fibroblasts that included alterations in energy metabolism, cell signaling and gene expression regulation, cytoskeleton formation and maintenance, and intracellular stress responses. The physiological validation of the predicted functional adaptations of human cultured fibroblasts to complex III deficiency confirmed the up-regulation of glycolytic enzyme activities and the accumulation of branched-chain among other amino acids, suggesting the activation of anaerobic glycolysis and cellular catabolic states, in particular protein catabolism, together with autophagy as adaptive responses to mitochondrial respiratory chain dysfunction and ATP deficiency. Our data point to an overall metabolic and genetic reprogramming that could contribute to explain the clinical manifestations of complex III deficiency in patients.
