A Case of Severe Hypermetabolism of Nonthyroid Origin With a Defect in the Maintenance of Mitochondrial Respiratory Control: A Correlated Clinical, Biochemical, and Morphological Study

Luft, Rolf; Ikkos, D; Palmieri, Genaro M. A.; Ernster, Lars; Afzelius, Björn A.

doi:10.1172/jci104637

Cited by 865 publications

(231 citation statements)

References 67 publications

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“…However, reported clinical cases of ATP depletion attributable to increased uncoupling of respiration are very rare. Uncoupling-mediated muscle atrophy in humans was first described by Luft and colleagues 8,9 in 1959 and was called Luft's disease. This disease is important not only because it was the first identified human mitochondrial disorder but also because Luft's disease is still the only mitochondrial disease caused by uncoupling of oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria in Luft's disease were highly variable in size and shape with a range of abnormal internal structures, including densely packed cristae, tubular structures, electron-dense regularly layered cores, and concentric structures. 9,10,39 In PGC-1␣ transgenic mice, such morphological abnormalities in mitochondria were not observed. The reasons for these differences are unknown.…”

Section: Discussionmentioning

confidence: 99%

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Overexpression of Peroxisome Proliferator-Activated Receptor γ Co-Activator-1α Leads to Muscle Atrophy with Depletion of ATP

Miura¹,

Tomitsuka

Kamei

et al. 2006

The American Journal of Pathology

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Peroxisome proliferator-activated receptor-␥ co-activator-1␣ (PGC-1␣) is a key nuclear receptor co-activator for mitochondrial biogenesis. Here we report that overexpression of PGC-1␣ in skeletal muscles increased mitochondrial number and caused atrophy of skeletal muscle, especially type 2B fiber-rich muscles (gastrocnemius, quadriceps, and plantaris). Muscle atrophy became evident at 25 weeks of age, and a portion of the muscle was replaced by adipocytes. Mice showed increased energy expenditure and reduced body weight; thyroid hormone levels were normal. Mitochondria exhibited normal respiratory chain activity per mitochondrion; however, mitochondrial respiration was not inhibited by an ATP synthase inhibitor, oligomycin, clearly indicating that oxidative phosphorylation was uncoupled. Accordingly, ATP content in gastrocnemius was markedly reduced. A similar phenotype is observed in Luft's disease, a mitochondrial disorder that involves increased uncoupling of respiration and muscle atrophy. Our results indicate that overexpression of PGC-1␣ in skeletal muscle increases not only mitochondrial biogenesis but also uncoupling of respiration, resulting in muscle atrophy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Overexpression of Peroxisome Proliferator-Activated Receptor γ Co-Activator-1α Leads to Muscle Atrophy with Depletion of ATP

Miura¹,

Tomitsuka

Kamei

et al. 2006

The American Journal of Pathology

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“…The first mitochondrial disease to be reported was Luft's disease, characterized by loose coupling between electron transport and ATP synthesis [3]. The patient consumed vast amounts of oxygen in the absence of corresponding ATP production and the generated energy was dissipated as heat leading to profuse perspiration.…”

Section: Classical Mitochondrial Diseasesmentioning

confidence: 99%

“…Surprisingly, most evidence today supports this original endosymbiont hypothesis and suggests that mitochondria indeed derive from ancient bacteria [2]. Mitochondria were the first cell organelle to be linked to human disease when Luft et al [3] in 1962 presented evidence for mitochondrial dysfunction in a patient with hypermetabolism. The role of mitochondria in human disease was further established by subsequent reports of deficient respiratory chain function and morphological aberrations of mitochondria in patients with different types of encephalomyopathic syndromes.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial medicine – recent advances

Graff

Clayton

Larsson

1999

Journal of Internal Medicine

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Abstract. Graff C, Clayton DA, Larsson N-G (Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden, and Howard Hughes Medical Institute, Chevy Chase, MD, USA). Mitochondrial medicine 2 recent advances (Review). J Intern Med 1999; 246: 11223.Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Mitochondrial DNA (mtDNA) encodes essential subunits of the respiratory chain and is thus critical for maintaining cellular energy production. The first pathogenic mtDNA mutations were reported in 1988, and today more than 50 diseasecausing mtDNA mutations have been identified. In addition, mtDNA mutations have been implicated in ageing and in common disorders such as diabetes mellitus, heart failure and Parkinson's disease. This review will summarize recent advances in the rapidly expanding field of mitochondrial medicine.

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“…The only convincing defect of oxidation/phosphorylation coupling remains '~nonthyroidal hypermetabolism," or Luft disease, whose historical importance as the first disease documentedly due to mitochondrial dysfunction (Luft et al, 1962) contrasts with its extreme rarity (two bona fide patients described). Both patients with Luft disease were sporadic cases and it is generally assumed that the defect involves a nuclear gene, although neither the gene nor the protein responsible for the "loose coupling" have been identified.…”

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confidence: 99%

Mitochondrial disorders

DiMauro

Tanji

1997

Jap J Human Genet

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SummaryIn this minireview, we attempt to survey the three main group of mitochondrial disorders, defects of nuclear DNA, defects of mitochondrial DNA, and defects of intergenomic signaling, with emphasis on recent contributions and pathogenetic mechanisms. In so doing, we have tried to point out some of the numerous unsolved problems in genotype/phenotype correlation and to indicate future directions of research. Key Words mitochondria, mitochondrial DNA, intergenomic signaling, respiratory chain, mitochondrial encephalomyopathiesThe fascinating and still unfolding story of mitochondrial disorders is not only a "tale of two genomes," but also a tale of their sometimes less than harmonious interaction. Thus, we have to review succinctly three types of human diseases: 1) Defects of nuclear genes, inherited as mendelian traits; 2) Defects of mitochondrial genes, which can be sporadic conditions or maternally-inherited disorders; and 3) Defects of intergenomic communication, in which the still unknown culprits are nuclear genes and inheritance is mendelian. Though in our review we will consider these three groups in sequence, a unified biomolecular classification of the mitochondrial disorders, including acquired conditions, is offered in Table I. Because of the concise nature of these minireviews, we will limit references to the most recent contributions. Other references are provided in recent comprehensive reviews, including three chapters in a row in the 2nd edition of The

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A Case of Severe Hypermetabolism of Nonthyroid Origin With a Defect in the Maintenance of Mitochondrial Respiratory Control: A Correlated Clinical, Biochemical, and Morphological Study

Cited by 865 publications

References 67 publications

Overexpression of Peroxisome Proliferator-Activated Receptor γ Co-Activator-1α Leads to Muscle Atrophy with Depletion of ATP

Overexpression of Peroxisome Proliferator-Activated Receptor γ Co-Activator-1α Leads to Muscle Atrophy with Depletion of ATP

Mitochondrial medicine – recent advances

Mitochondrial disorders

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