15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mitochondrial regulation of β-cell function: maintaining the momentum for insulin release

      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

          All forms of diabetes share the common etiology of insufficient pancreatic β-cell function to meet peripheral insulin demand. In pancreatic β-cells, mitochondria serve to integrate the metabolism of exogenous nutrients into energy output, which ultimately leads to insulin release. As such, mitochondrial dysfunction underlies β-cell failure and the development of diabetes. Mitochondrial regulation of β-cell function occurs through many diverse pathways, including metabolic coupling, generation of reactive oxygen species, maintenance of mitochondrial mass, and through interaction with other cellular organelles. In this chapter, we will focus on the importance of enzymatic regulators of mitochondrial fuel metabolism and control of mitochondrial mass to pancreatic β-cell function, describing how defects in these pathways ultimately lead to diabetes. Furthermore, we will examine the factors responsible for mitochondrial biogenesis and degradation and their roles in the balance of mitochondrial mass in β-cells. Clarifying the causes of β-cell mitochondrial dysfunction may inform new approaches to treat the underlying etiologies of diabetes.

          Related collections

          Most cited references 113

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

          Essential role for Nix in autophagic maturation of erythroid cells.

          Erythroid cells undergo enucleation and the removal of organelles during terminal differentiation. Although autophagy has been suggested to mediate the elimination of organelles for erythroid maturation, the molecular mechanisms underlying this process remain undefined. Here we report a role for a Bcl-2 family member, Nix (also called Bnip3L), in the regulation of erythroid maturation through mitochondrial autophagy. Nix(-/-) mice developed anaemia with reduced mature erythrocytes and compensatory expansion of erythroid precursors. Erythrocytes in the peripheral blood of Nix(-/-) mice exhibited mitochondrial retention and reduced lifespan in vivo. Although the clearance of ribosomes proceeded normally in the absence of Nix, the entry of mitochondria into autophagosomes for clearance was defective. Deficiency in Nix inhibited the loss of mitochondrial membrane potential (DeltaPsi(m)), and treatment with uncoupling chemicals or a BH3 mimetic induced the loss of DeltaPsi(m) and restored the sequestration of mitochondria into autophagosomes in Nix(-/-) erythroid cells. These results suggest that Nix-dependent loss of DeltaPsi(m) is important for targeting the mitochondria into autophagosomes for clearance during erythroid maturation, and interference with this function impairs erythroid maturation and results in anaemia. Our study may also provide insights into molecular mechanisms underlying mitochondrial quality control involving mitochondrial autophagy.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Transcriptional regulatory circuits controlling mitochondrial biogenesis and function.

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

              Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.

              Leber's hereditary optic neuropathy is a maternally inherited disease resulting in optic nerve degeneration and cardiac dysrhythmia. A mitochondrial DNA replacement mutation was identified that correlated with this disease in multiple families. This mutation converted a highly conserved arginine to a histidine at codon 340 in the NADH dehydrogenase subunit 4 gene and eliminated an Sfa NI site, thus providing a simple diagnostic test. This finding demonstrated that a nucleotide change in a mitochondrial DNA energy production gene can result in a neurological disease.
                Bookmark

                Author and article information

                Journal
                7603128
                5672
                Mol Aspects Med
                Mol. Aspects Med.
                Molecular aspects of medicine
                0098-2997
                1872-9452
                7 February 2015
                7 February 2015
                April 2015
                01 April 2016
                : 42
                : 91-104
                Affiliations
                [1 ]Division of Cardiology, Vascular Medicine Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
                [2 ]Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
                [3 ]Division of Metabolism, Endocrinology & Diabetes and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
                Author notes
                [** ] Corresponding author: Scott A. Soleimanpour, 1000 Wall Street, Brehm Tower Room 5317, Ann Arbor, MI 48105, Phone: (734) 763-0528, ssol@ 123456med.umich.edu
                Article
                NIHMS661745
                10.1016/j.mam.2015.01.004
                4404204
                25659350
                © 2015 Published by Elsevier Ltd.

                This manuscript version is made available under the CC BY-NC-ND 4.0 license.

                Categories
                Article

                islet, diabetes, mitochondria, mtdna, mitophagy, metabolism

                Comments

                Comment on this article