ArticleThe Journal of biological chemistry2008
Early mitochondrial dysfunction in long-lived Mclk1+/- mice.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 211 citations in OpenAlex.
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- Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial immunometabolic modulation.PLoS pathogens · 2023Article
- New Insights on the Uptake and Trafficking of Coenzyme Q.Antioxidants (Basel, Switzerland) · 2023Review
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- Systemic Metabolism and Mitochondria in the Mechanism of Alzheimer's Disease: Finding Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Antimicrobial mitochondrial reactive oxygen species induction by lung epithelial metabolic reprogramming.bioRxiv : the preprint server for biology · 2023Article
- Therapeutic Stimulation of Glycolytic ATP Production for Treating ROS-Mediated Cellular Senescence.Metabolites · 2022Article
- CoQNutrients · 2022Review
- Long-term sulforaphane-treatment restores redox homeostasis and prevents cognitive decline in middleaged female and male rats, but cannot revert previous damage in old animals.Biogerontology · 2022Article
- Reduced expression of mitochondrial complex I subunit Ndufs2 does not impact healthspan in mice.Scientific reports · 2022Article
- Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis.Nature communications · 2022Article
- Mitochondrial complex I as a therapeutic target for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
- Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reduced activity of CLK-1/MCLK1 (also known as COQ7), a mitochondrial enzyme that is necessary for ubiquinone biosynthesis, prolongs the lifespan of nematodes and mice by a mechanism that is distinct from that of the insulin signaling pathway. Here we show that 2-fold reduction of MCLK1 expression in mice reveals an additional function for the protein, as this level of reduction does not affect ubiquinone levels yet affects mitochondrial function substantially. Indeed, we observe that the phenotype of young Mclk1(+/-) mutants includes a severe reduction of mitochondrial electron transport, ATP synthesis, and total nicotinamide adenine dinucleotide (NAD(tot)) pool size as well as an alteration in the activity of key enzymes of the tricarboxylic acid cycle. Surprisingly, we also find that Mclk1 heterozygosity leads to a dramatic increase in mitochondrial oxidative stress by a variety of measures. Furthermore, we find that the mitochondrial dysfunction is accompanied by a decrease in oxidative damage to cytosolic proteins as well as by a decrease in plasma isoprostanes, a systemic biomarker of oxidative stress and aging. We propose a mechanism for the conjunction of low ATP levels, high mitochondrial oxidative stress, and low non-mitochondrial oxidative damage in a long-lived mutant. Our model helps to clarify the relationship between energy metabolism and the aging process and suggests the need for a reformulation of the mitochondrial oxidative stress theory of aging.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.