Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes
Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese p...
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| Format: | Article |
| Language: | English |
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Elsevier
2017-04-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231716303457 |
| _version_ | 1811327788943147008 |
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| author | María Gómez-Serrano Emilio Camafeita Juan A. López Miguel A. Rubio Irene Bretón Inés García-Consuegra Eva García-Santos Jesús Lago Andrés Sánchez-Pernaute Antonio Torres Jesús Vázquez Belén Peral |
| author_facet | María Gómez-Serrano Emilio Camafeita Juan A. López Miguel A. Rubio Irene Bretón Inés García-Consuegra Eva García-Santos Jesús Lago Andrés Sánchez-Pernaute Antonio Torres Jesús Vázquez Belén Peral |
| author_sort | María Gómez-Serrano |
| collection | DOAJ |
| description | Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry. The alterations undergone by the mitochondrial proteome revealed aging- and T2DM-specific hallmarks. Thus, while a global decrease of oxidative phosphorylation (OXPHOS) subunits was found in aging, the diabetic patients exhibited a reduction of specific OXPHOS complexes as well as an up-regulation of the anti-oxidant response. Under both conditions, evidence is shown for the first time of a link between increased thiol protein oxidation and decreased protein abundance in adipose tissue mitochondria. This association was stronger in T2DM, where OXPHOS mitochondrial- vs. nuclear-encoded protein modules were found altered, suggesting impaired mitochondrial protein translocation and complex assembly. The marked down-regulation of OXPHOS oxidized proteins and the alteration of oxidized Cys residues related to protein import through the redox-active MIA (Mitochondrial Intermembrane space Assembly) pathway support that defects in protein translocation to the mitochondria may be an important underlying mechanism for mitochondrial dysfunction in T2DM and physiological aging. The present draft of redox targets together with the quantification of protein and oxidative changes may help to better understand the role of oxidative stress in both a physiological process like aging and a pathological condition like T2DM. Keywords: Adipose tissue, Mitochondria, OXPHOS, Redox proteomics, Thiol oxidation, Type 2 diabetes |
| first_indexed | 2024-04-13T15:14:18Z |
| format | Article |
| id | doaj.art-482a85d67e6a419eae8f94e6f8e0f5ca |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T15:14:18Z |
| publishDate | 2017-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-482a85d67e6a419eae8f94e6f8e0f5ca2022-12-22T02:41:54ZengElsevierRedox Biology2213-23172017-04-0111415428Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetesMaría Gómez-Serrano0Emilio Camafeita1Juan A. López2Miguel A. Rubio3Irene Bretón4Inés García-Consuegra5Eva García-Santos6Jesús Lago7Andrés Sánchez-Pernaute8Antonio Torres9Jesús Vázquez10Belén Peral11Instituto de Investigaciones Biomédicas, Alberto Sols, (IIBM); Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid (CSIC-UAM), Madrid 28029, SpainLaboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, SpainLaboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, SpainDepartment of Endocrinology, Hospital Clínico San Carlos (IDISSC), Facultad de Medicina, Universidad Complutense, Madrid 28040, SpainDepartment of Endocrinology and Nutrition, Hospital General Universitario Gregorio Marañón (IISGM), Madrid 28007, SpainInstituto de Investigación, Hospital Universitario 12 de Octubre (i+12), Madrid 28041, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Madrid 28029, SpainInstituto de Investigaciones Biomédicas, Alberto Sols, (IIBM); Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid (CSIC-UAM), Madrid 28029, SpainDepartment of Surgery, Hospital General Universitario Gregorio Marañón (IISGM), Madrid 28007, SpainDepartment of Surgery, Hospital Clínico San Carlos (IDISSC), Facultad de Medicina, Universidad Complutense, Madrid 28040, SpainDepartment of Surgery, Hospital Clínico San Carlos (IDISSC), Facultad de Medicina, Universidad Complutense, Madrid 28040, SpainLaboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, SpainInstituto de Investigaciones Biomédicas, Alberto Sols, (IIBM); Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid (CSIC-UAM), Madrid 28029, Spain; Correspondence to: Instituto de Investigaciones Biomédicas, Alberto Sols (IIBM), Consejo Superior de Investigaciones Científicas (CSIC) and Universidad Autónoma de Madrid (UAM), Arturo Duperier, 4, E-28029 Madrid, SpainHuman age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry. The alterations undergone by the mitochondrial proteome revealed aging- and T2DM-specific hallmarks. Thus, while a global decrease of oxidative phosphorylation (OXPHOS) subunits was found in aging, the diabetic patients exhibited a reduction of specific OXPHOS complexes as well as an up-regulation of the anti-oxidant response. Under both conditions, evidence is shown for the first time of a link between increased thiol protein oxidation and decreased protein abundance in adipose tissue mitochondria. This association was stronger in T2DM, where OXPHOS mitochondrial- vs. nuclear-encoded protein modules were found altered, suggesting impaired mitochondrial protein translocation and complex assembly. The marked down-regulation of OXPHOS oxidized proteins and the alteration of oxidized Cys residues related to protein import through the redox-active MIA (Mitochondrial Intermembrane space Assembly) pathway support that defects in protein translocation to the mitochondria may be an important underlying mechanism for mitochondrial dysfunction in T2DM and physiological aging. The present draft of redox targets together with the quantification of protein and oxidative changes may help to better understand the role of oxidative stress in both a physiological process like aging and a pathological condition like T2DM. Keywords: Adipose tissue, Mitochondria, OXPHOS, Redox proteomics, Thiol oxidation, Type 2 diabeteshttp://www.sciencedirect.com/science/article/pii/S2213231716303457 |
| spellingShingle | María Gómez-Serrano Emilio Camafeita Juan A. López Miguel A. Rubio Irene Bretón Inés García-Consuegra Eva García-Santos Jesús Lago Andrés Sánchez-Pernaute Antonio Torres Jesús Vázquez Belén Peral Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes Redox Biology |
| title | Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes |
| title_full | Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes |
| title_fullStr | Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes |
| title_full_unstemmed | Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes |
| title_short | Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes |
| title_sort | differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity associated aging and diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2213231716303457 |
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