27
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Role of Mitochondria in Reactive Oxygen Species Generation and Its Implications for Neurodegenerative Diseases

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Mitochondria are dynamic cellular organelles that consistently migrate, fuse, and divide to modulate their number, size, and shape. In addition, they produce ATP, reactive oxygen species, and also have a biological role in antioxidant activities and Ca 2+ buffering. Mitochondria are thought to play a crucial biological role in most neurodegenerative disorders. Neurons, being high-energy-demanding cells, are closely related to the maintenance, dynamics, and functions of mitochondria. Thus, impairment of mitochondrial activities is associated with neurodegenerative diseases, pointing to the significance of mitochondrial functions in normal cell physiology. In recent years, considerable progress has been made in our knowledge of mitochondrial functions, which has raised interest in defining the involvement of mitochondrial dysfunction in neurodegenerative diseases. Here, we summarize the existing knowledge of the mitochondrial function in reactive oxygen species generation and its involvement in the development of neurodegenerative diseases.

          Related collections

          Most cited references95

          • Record: found
          • Abstract: found
          • Article: not found

          The sites and topology of mitochondrial superoxide production.

          Mitochondrial superoxide production is an important source of reactive oxygen species in cells, and may cause or contribute to ageing and the diseases of ageing. Seven major sites of superoxide production in mammalian mitochondria are known and widely accepted. In descending order of maximum capacity they are the ubiquinone-binding sites in complex I (site IQ) and complex III (site IIIQo), glycerol 3-phosphate dehydrogenase, the flavin in complex I (site IF), the electron transferring flavoprotein:Q oxidoreductase (ETFQOR) of fatty acid beta-oxidation, and pyruvate and 2-oxoglutarate dehydrogenases. None of these sites is fully characterized and for some we only have sketchy information. The topology of the sites is important because it determines whether or not a site will produce superoxide in the mitochondrial matrix and be able to damage mitochondrial DNA. All sites produce superoxide in the matrix; site IIIQo and glycerol 3-phosphate dehydrogenase also produce superoxide to the intermembrane space. The relative contribution of each site to mitochondrial reactive oxygen species generation in the absence of electron transport inhibitors is unknown in isolated mitochondria, in cells or in vivo, and may vary considerably with species, tissue, substrate, energy demand and oxygen tension. Copyright (c) 2010 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Mitochondrial Cristae: Where Beauty Meets Functionality.

            Mitochondrial cristae are dynamic bioenergetic compartments whose shape changes under different physiological conditions. Recent discoveries have unveiled the relation between cristae shape and oxidative phosphorylation (OXPHOS) function, suggesting that membrane morphology modulates the organization and function of the OXPHOS system, with a direct impact on cellular metabolism. As a corollary, cristae-shaping proteins have emerged as potential modulators of mitochondrial bioenergetics, a concept confirmed by genetic experiments in mouse models of respiratory chain deficiency. Here, we review our knowledge of mitochondrial ultrastructural organization and how it impacts mitochondrial metabolism.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mitochondrial oxidative stress: implications for cell death.

              In addition to the established role of the mitochondria in energy metabolism, regulation of cell death has emerged as a second major function of these organelles. This seems to be intimately linked to their generation of reactive oxygen species (ROS), which have been implicated in mtDNA mutations, aging, and cell death. Mitochondrial regulation of apoptosis occurs by mechanisms, which have been conserved through evolution. Thus, many lethal agents target the mitochondria and cause release of cytochrome c and other pro-apoptotic proteins into the cytoplasm. Cytochrome c release is initiated by the dissociation of the hemoprotein from its binding to the inner mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and increases the level of soluble cytochrome c in the intermembrane space. Subsequent release of the hemoprotein occurs by pore formation mediated by pro-apoptotic Bcl-2 family proteins, or by Ca(2+) and ROS-triggered mitochondrial permeability transition, although the latter pathway might be more closely associated with necrosis. Taken together, these findings have placed the mitochondria in the focus of current cell death research.
                Bookmark

                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                17 December 2018
                December 2018
                : 7
                : 12
                : 274
                Affiliations
                [1 ]State Key Laboratory of Silkworm Genome Biology, Southwest University, Beibei, Chongqing 400716, China; drkausarsn@ 123456hotmail.com (S.K.); fengwang_swu@ 123456163.com (F.W.)
                [2 ]Engineering Research Center for Cancer Biomedical and Translational Medicine, Southwest University, Beibei, Chongqing 400716, China
                [3 ]Chongqing Engineering and Technology Research Center for Silk Biomaterials and Regenerative Medicine, Southwest University, Beibei, Chongqing 400716, China
                Author notes
                [* ]Correspondence: hcui@ 123456swu.edu.cn ; Tel.: +86-23-68251713; Fax: +86-23-68251128
                Article
                cells-07-00274
                10.3390/cells7120274
                6316843
                30563029
                eaf7f9a3-2bfe-4966-8d0d-b41b9c4e71de
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 November 2018
                : 14 December 2018
                Categories
                Review

                electron transport chain,mitochondria,neurodegenerative diseases,oxidative damage

                Comments

                Comment on this article