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      Mitoproteomics: Tackling Mitochondrial Dysfunction in Human Disease

      1 , 2 , 2 , 3 , 1 , 4

      Oxidative Medicine and Cellular Longevity

      Hindawi Limited

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          Abstract

          Mitochondria are highly dynamic and regulated organelles that historically have been defined based on their crucial role in cell metabolism. However, they are implicated in a variety of other important functions, making mitochondrial dysfunction an important axis in several pathological contexts. Despite that conventional biochemical and molecular biology approaches have provided significant insight into mitochondrial functionality, innovative techniques that provide a global view of the mitochondrion are still necessary. Proteomics fulfils this need by enabling accurate, systems-wide quantitative analysis of protein abundance. More importantly, redox proteomics approaches offer unique opportunities to tackle oxidative stress, a phenomenon that is intimately linked to aging, cardiovascular disease, and cancer. In addition, cutting-edge proteomics approaches reveal how proteins exert their functions in complex interaction networks where even subtle alterations stemming from early pathological states can be monitored. Here, we describe the proteomics approaches that will help to deepen the role of mitochondria in health and disease by assessing not only changes to mitochondrial protein composition but also alterations to their redox state and how protein interaction networks regulate mitochondrial function and dynamics. This review is aimed at showing the reader how the application of proteomics approaches during the last 20 years has revealed crucial mitochondrial roles in the context of aging, neurodegenerative disorders, metabolic disease, and cancer.

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          Most cited references 317

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              The hallmarks of aging.

              Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Oxidative Medicine and Cellular Longevity
                Oxidative Medicine and Cellular Longevity
                Hindawi Limited
                1942-0900
                1942-0994
                November 08 2018
                November 08 2018
                : 2018
                : 1-26
                Affiliations
                [1 ]Laboratory of Cardiovascular Proteomics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain
                [2 ]Centro de Investigación Biomédica en Red sobre Enfermedades Cardiovasculares (CIBERCV), Spain
                [3 ]Proteomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain
                [4 ]Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), Consejo Superior de Investigaciones Científicas & Universidad Autónoma de Madrid (CSIC-UAM), 28029 Madrid, Spain
                Article
                10.1155/2018/1435934
                6250043
                © 2018

                http://creativecommons.org/licenses/by/4.0/

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