2026-06-14T03:44:03Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/51252024-10-31T11:40:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
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
10.1016/j.redox.2016.12.013
2213-2317
Redox Biology
28064117
http://hdl.handle.net/20.500.12105/5125
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
https://repisalud.isciii.es/bitstreams/d858046f-7a4d-4e4e-9f3b-b7016c6731ee/download
File
MD5
4aaa37e50f92506f4d4eaa4a9862bef2
2568561
application/pdf
DifferentialProteomicAndOxidative_2017
URL
https://repisalud.isciii.es/bitstreams/d5037022-6b48-4323-a8ed-cdd87bddc1db/download
File
MD5
69d32fa2aac95eaf333539b050177cc4
1138579
application/pdf
DifferentialProteomicAndOxidative_2017_Supp
URL
https://repisalud.isciii.es/bitstreams/96fcdad6-0ca6-4fe0-9ee3-62dae49f613a/download
File
MD5
5a78c1a200379287768d8716c0c7b6ef
3401728
application/vnd.ms-excel
DifferentialProteomicAndOxidative_2017_Data1
URL
https://repisalud.isciii.es/bitstreams/b8861aba-1028-4b91-9c97-dcf232422b5a/download
File
MD5
e3215f3d61e24bb1a8f28d1050d3ad6f
257024
application/vnd.ms-excel
DifferentialProteomicAndOxidative_2017_Data2
URL
https://repisalud.isciii.es/bitstreams/d715e093-2917-4f07-97aa-09e8e270817b/download
File
MD5
403efe9a7c683a4b13b32a4b8b6404c3
87040
application/vnd.ms-excel
DifferentialProteomicAndOxidative_2017_Data3
URL
https://repisalud.isciii.es/bitstreams/7c6d312c-d8d2-4be0-b24d-6b9998376237/download
File
MD5
5da79e2c7bc417ff8d18f1af66b4e498
45568
application/vnd.ms-excel
DifferentialProteomicAndOxidative_2017_Data4
URL
https://repisalud.isciii.es/bitstreams/c18d0eca-95db-4c0e-a6f7-eaf29966bb11/download
File
MD5
62289ea6df2a8992892f3eb8963df929
76056
text/plain
DifferentialProteomicAndOxidative_2017.txt
URL
https://repisalud.isciii.es/bitstreams/d9454b64-8752-4ef9-8404-1575dee73b4a/download
File
MD5
28fee1efb18dad0d7db1ab66727dc5e0
10962
text/plain
DifferentialProteomicAndOxidative_2017_Supp.txt
URL
https://repisalud.isciii.es/bitstreams/b5fb1f40-d385-4429-85c0-c60e9fba58a0/download
File
MD5
3cc298e3aae7fb65fa41468e4a374bdc
100000
text/plain
DifferentialProteomicAndOxidative_2017_Data1.txt
URL
https://repisalud.isciii.es/bitstreams/c81bdc18-281c-450d-92df-6eb2c771a14a/download
File
MD5
1c3b5a023c8c9071ca942f1839dfa40e
100002
text/plain
DifferentialProteomicAndOxidative_2017_Data2.txt
URL
https://repisalud.isciii.es/bitstreams/261244b2-6e02-4bdd-864d-460b8ed38de8/download
File
MD5
c014c8feae16e76605c5e0b0b65b79b4
39353
text/plain
DifferentialProteomicAndOxidative_2017_Data3.txt
URL
https://repisalud.isciii.es/bitstreams/7256b8ce-6e04-4045-afab-2fe5175a8ea3/download
File
MD5
4de1993f0a9935b82f6ead0be1cb9899
21362
text/plain
DifferentialProteomicAndOxidative_2017_Data4.txt