Bioenergetics of mitochondrial diseases associated with mtDNA mutations

Giorgio Lenaz, Alessandra Baracca, Valerio Carelli, Marilena D'Aurelio, Gianluca Sgarbi, Giancarlo Solaini

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

This mini-review summarizes our present view of the biochemical alterations associated with mitochondrial DNA (mtDNA) point mutations. Mitochondrial cytopathies caused by mutations of mtDNA are well-known genetic and clinical entities, but the biochemical pathogenic mechanisms are often obscure. Leber's hereditary optic neuropathy (LHON) is due to three main mutations in genes for complex I subunits. Even if the catalytic activity of complex I is maintained except in cells carrying the 3460/ND1 mutation, in all cases there is a change in sensitivity to complex I inhibitors and an impairment of mitochondrial respiration, eliciting the possibility of generation of reactive oxygen species (ROS) by the complex. Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa (NARP), is due to a mutation in the ATPase-6 gene. In NARP patients ATP synthesis is strongly depressed to an extent proportional to the mutation load; nevertheless, ATP hydrolysis and ATP-driven proton translocation are not affected. It is suggested that the NARP mutation affects the ability of the enzyme to couple proton transport to ATP synthesis. A point mutation in subunit III of cytochrome c oxidase is accompanied by a syndrome resembling MELAS: however, no major biochemical defect is found, if we except an enhanced production of ROS. The mechanism of such enhancement is at present unknown. In this review, we draw attention to a few examples in which the overproduction of ROS might represent a common step in the induction of clinical phenotypes and/or in the progression of several human pathologies associated with mtDNA point mutations.

Original languageEnglish
Pages (from-to)89-94
Number of pages6
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1658
Issue number1-2
DOIs
Publication statusPublished - Jul 23 2004

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Mitochondrial Diseases
Mitochondrial DNA
Energy Metabolism
Adenosine Triphosphate
Muscle
Reactive Oxygen Species
Mutation
Point Mutation
Protons
Genes
Pathology
Electron Transport Complex IV
MELAS Syndrome
Leber's Hereditary Optic Atrophy
Adenosine Triphosphatases
Hydrolysis
Optics
Catalyst activity
Defects
Respiration

Keywords

  • ATP synthase
  • Complex I
  • Cytochrome oxidase subunit III
  • LHON
  • Mitochondrial cytopathy
  • NARP

ASJC Scopus subject areas

  • Biophysics

Cite this

Bioenergetics of mitochondrial diseases associated with mtDNA mutations. / Lenaz, Giorgio; Baracca, Alessandra; Carelli, Valerio; D'Aurelio, Marilena; Sgarbi, Gianluca; Solaini, Giancarlo.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1658, No. 1-2, 23.07.2004, p. 89-94.

Research output: Contribution to journalArticle

Lenaz, Giorgio ; Baracca, Alessandra ; Carelli, Valerio ; D'Aurelio, Marilena ; Sgarbi, Gianluca ; Solaini, Giancarlo. / Bioenergetics of mitochondrial diseases associated with mtDNA mutations. In: Biochimica et Biophysica Acta - Bioenergetics. 2004 ; Vol. 1658, No. 1-2. pp. 89-94.
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