Blog
About

741
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Mitochondrial genetics

      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

          Introduction

          In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders.

          Sources of data

          In this article, a review of the current mitochondrial genetics literature was conducted using PubMed ( http://www.ncbi.nlm.nih.gov/pubmed/). In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (www.mitomap.org), the Human DNA polymerase Gamma Mutation Database ( http://tools.niehs.nih.gov/polg/) and PhyloTree.org (www.phylotree.org), a repository of global mtDNA variation.

          Areas of agreement

          The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases.

          Areas of controversy

          The exact mechanisms which govern the inheritance of mtDNA are hotly debated.

          Growing points

          Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease.

          Related collections

          Most cited references 173

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

          Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA.

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

            Mitochondrial fission, fusion, and stress.

            Mitochondrial fission and fusion play critical roles in maintaining functional mitochondria when cells experience metabolic or environmental stresses. Fusion helps mitigate stress by mixing the contents of partially damaged mitochondria as a form of complementation. Fission is needed to create new mitochondria, but it also contributes to quality control by enabling the removal of damaged mitochondria and can facilitate apoptosis during high levels of cellular stress. Disruptions in these processes affect normal development, and they have been implicated in neurodegenerative diseases, such as Parkinson's.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A mitochondrial protein compendium elucidates complex I disease biology.

              Mitochondria are complex organelles whose dysfunction underlies a broad spectrum of human diseases. Identifying all of the proteins resident in this organelle and understanding how they integrate into pathways represent major challenges in cell biology. Toward this goal, we performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes and their protein expression across 14 mouse tissues. We link poorly characterized proteins in this inventory to known mitochondrial pathways by virtue of shared evolutionary history. Using this approach, we predict 19 proteins to be important for the function of complex I (CI) of the electron transport chain. We validate a subset of these predictions using RNAi, including C8orf38, which we further show harbors an inherited mutation in a lethal, infantile CI deficiency. Our results have important implications for understanding CI function and pathogenesis and, more generally, illustrate how our compendium can serve as a foundation for systematic investigations of mitochondria.
                Bookmark

                Author and article information

                Affiliations
                Institute of Genetic Medicine, International Centre for Life, Newcastle University , Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
                Author notes
                [* ]Correspondence address. Institute of Genetic Medicine, International Centre for Life, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK. E-mail: gavin.hudson@ 123456ncl.ac.uk
                Journal
                Br Med Bull
                Br. Med. Bull
                brimed
                bmbull
                British Medical Bulletin
                Oxford University Press
                0007-1420
                1471-8391
                June 2013
                June 2013
                : 106
                : 1
                : 135-159
                23704099
                3675899
                10.1093/bmb/ldt017
                ldt017
                © The Author 2013. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                Product
                Categories
                Articles

                Medicine

                mitochondria, mtdna, mitochondrial disease, mitochondrial dna, genetics

                Comments

                Comment on this article