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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 references249

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              Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics.

              Quantitative proteomics has traditionally been performed by two-dimensional gel electrophoresis, but recently, mass spectrometric methods based on stable isotope quantitation have shown great promise for the simultaneous and automated identification and quantitation of complex protein mixtures. Here we describe a method, termed SILAC, for stable isotope labeling by amino acids in cell culture, for the in vivo incorporation of specific amino acids into all mammalian proteins. Mammalian cell lines are grown in media lacking a standard essential amino acid but supplemented with a non-radioactive, isotopically labeled form of that amino acid, in this case deuterated leucine (Leu-d3). We find that growth of cells maintained in these media is no different from growth in normal media as evidenced by cell morphology, doubling time, and ability to differentiate. Complete incorporation of Leu-d3 occurred after five doublings in the cell lines and proteins studied. Protein populations from experimental and control samples are mixed directly after harvesting, and mass spectrometric identification is straightforward as every leucine-containing peptide incorporates either all normal leucine or all Leu-d3. We have applied this technique to the relative quantitation of changes in protein expression during the process of muscle cell differentiation. Proteins that were found to be up-regulated during this process include glyceraldehyde-3-phosphate dehydrogenase, fibronectin, and pyruvate kinase M2. SILAC is a simple, inexpensive, and accurate procedure that can be used as a quantitative proteomic approach in any cell culture system.
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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
                43dcc7d6-c09c-4530-8538-d07e1cbbe724
                © 2018

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

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