Elsevier

Metabolism

Volume 46, Issue 3, March 1997, Pages 306-321
Metabolism

Review article
Lactic acidosis and other mitochondrial disorders

https://doi.org/10.1016/S0026-0495(97)90259-6Get rights and content

Abstract

The ability of mitochondria to oxidize substrates and generate energy is integral to normal homeostasis and to the ability of cells to survive in the face of impending energy failure. Lactic acidosis is a common and readily apparent biochemical marker for mitochondrial dysfunction. However, lactic acidosis represents only the most obvious example in which acquired or congenital abnormalities of mitochondrial oxidative phosphorylating capacity contribute to the pathobiology and phenotypic expression of a broad spectrum of clinical disorders. Consequently, interventions that improve mitochondrial function or prevent mitochondrial energy failure may have widespread therapeutic implications.

References (222)

  • I Trounce et al.

    Decline in skeletal muscle mitochondrial respiratory chain function: Possible factor in aging

    Lancet

    (1989)
  • D Curti et al.

    Age-related modifications of cytochrome C oxidase activity in discrete brain regions

    Mech Aging Dev

    (1990)
  • G Paradies et al.

    Age-related changes in the activity of the pyruvate carrier and in the lipid composition in rat-heart mitochondria

    Biochim Biophys Acta

    (1990)
  • E Bogonez et al.

    Pyruvate dehydrogenase dephosphorylation in rat brain synaptosomes and mitochondria: Evidence for a calcium-mediated effect in response to depolarization, and variations due to aging

    Neurosci Lett

    (1992)
  • JM Cooper et al.

    Analyses of mitochondrial respiratory chain function and mitochondrial DNA deletion in human skeletal muscle: Effect of ageing

    J Neurol Sci

    (1992)
  • AL Sylvia et al.

    Effects of age on brain oxidative metabolism in vivo

    Brain Res

    (1979)
  • J Muller-Hocker

    Cytochrome C oxidase deficient fibres in the limb muscle and diaphragm of man without muscular disease: An age-related alteration

    J Neurol Sci

    (1990)
  • AW Linnane et al.

    Mitochondrial DNA mutations as an important contributor to aging and degenerative diseases

    Lancet

    (1989)
  • K Hattori et al.

    Age-dependent increase in deleted mitochondrial DNA in the human heart: Possible contributory factor to presbycardia

    Am Heart J

    (1991)
  • M Hayakawa et al.

    Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm

    Biochem Biophys Res Commun

    (1991)
  • W Reardon et al.

    Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA

    Lancet

    (1992)
  • T Awata et al.

    Japanese case of diabetes mellitus and deafness with mutation in mitochondrial tRNALeu(UUR) gene

    Lancet

    (1993)
  • K-D Gerbitz et al.

    Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALeu(UUR) gene

    FEBS Lett

    (1993)
  • Y Oka et al.

    Mitochondrial gene mutation in islet-cell-antibody-positive patients who were initially non-insulin-dependent diabetics

    Lancet

    (1993)
  • K-D Gerbitz et al.

    Diabetes mellitus is one of the heterogeneous phenotypic features of a mitochondrial DNA point mutation within the tRNALEU(UUR) gene

    FEBS Lett

    (1993)
  • R Bolli

    Oxygen-derived free radicals and postischemic myocardial dysfunction (“stunned myocardium”)

    J Am Coll Cardiol

    (1988)
  • SL Marklund

    Role of toxic effects of oxygen in reperfusion damage

    J Mol Cell Cardiol

    (1988)
  • B Halliwell et al.

    Oxygen radicals and the nervous system

    Trends Neurosci

    (1985)
  • B Halliwell et al.

    Role of free radicals and catalytic metal ions in human disease: An overview

    Methods Enzymol

    (1990)
  • R Ferrari et al.

    Oxygen-mediated myocardial damage during ischaemia and reperfusion: Role of the cellular defenses against oxygen toxicity

    J Mol Cell Cardiol

    (1985)
  • BH Robinson

    Lactic acidemia

  • PW Stacpoole et al.

    A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults

    N Engl J Med

    (1992)
  • Y Hatefi

    The mitochondrial electron transport and oxidative phosphorylation system

    Annu Rev Biochem

    (1985)
  • H Sies et al.

    A role of mitochondrial glutathione peroxidase in modulating mitochondrial oxidations in liver

    Eur J Biochem

    (1978)
  • BG Barrell et al.

    A different genetic code in human mitochondria

    Nature

    (1979)
  • S Anderson et al.

    Sequence and organization of the human mitochondrial genome

    Nature

    (1981)
  • G Attardi

    Biogenesis of mitochondria

    Annu Rev Cell Biol

    (1988)
  • JC Avise

    Ten unorthodox perspectives on evolution prompted by comparative population genetic findings on mitochondrial DNA

    Annu Rev Genet

    (1991)
  • LA Glover et al.

    Targeting proteins to mitochondria: A current overview

    Biochem J

    (1992)
  • LB Arey

    The reproductive organs and sex cells, in Developmental Anatomy

    (1962)
  • DC Wallace

    Mitochondrial genetics: A paradigm for aging and degenerative diseases?

    Science

    (1992)
  • DC Wallace

    Diseases of the mitochondrial DNA

    Annu Rev Biochem

    (1992)
  • JM Shoffner et al.

    Oxidative phosphorylation diseases

  • B Halliwell

    Reactive oxygen species and the central nervous system

    J Neurochem

    (1992)
  • H-J Tritschler et al.

    Mitochondrial DNA alterations as a source of human disorders

    Neurology

    (1993)
  • TC Vary et al.

    Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver

    Am J Physiol

    (1986)
  • G Chattha et al.

    Lactic acidosis complicating the acquired immunodeficiency syndrome

    Ann Intern Med

    (1993)
  • C Mhiri et al.

    Zidovudine myopathy: A distinctive disorder associated with mitochondrial dysfunction

    Ann Neurol

    (1991)
  • D Harman

    The biologic clock: The mitochondria?

    J Am Geriatr Soc

    (1970)
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