2024-03-29T14:57:32Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/51252023-04-19T12:59:53Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2152col_20.500.12105_2146col_20.500.12105_2153
Repisalud
author
Gomez-Serrano, Maria
author
Camafeita, Emilio
author
Lopez, Juan Antonio
author
Rubio, Miguel A.
author
Breton, Irene
author
Garcia-Consuegra, Ines
author
Garcia-Santos, Eva
author
Lago, Jesus
author
Sanchez-Pernaute, Andres
author
Torres, Antonio
author
Vazquez, Jesus
author
Peral, Belen
funder
Ministerio de Economía, Industria y Competitividad (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Autonomous University of Madrid (España)
funder
Instituto de Salud Carlos III
funder
Fundación ProCNIC
2017-10-20T10:23:13Z
2017-10-20T10:23:13Z
2017
Redox Biol. 2017; 11:415-428
2213-2317
http://hdl.handle.net/20.500.12105/5125
28064117
10.1016/j.redox.2016.12.013
Redox Biology
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.
eng
Adipose tissue
Mitochondria
OXPHOS
Redox proteomics
Thiol oxidation
Type 2 diabetes
CYTOCHROME-C-OXIDASE
WHITE ADIPOSE-TISSUE
COMPLEX-I
INSULIN-RESISTANCE
QUANTITATIVE PROTEOMICS
TRANSCRIPTION FACTOR
MASS-SPECTROMETRY
REDOX PROTEOMICS
EXPRESSION
DISEASE
Differential proteomic and oxidative profiles unveil dysfunctional protein import to adipocyte mitochondria in obesity-associated aging and diabetes
journal article
URL
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