Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis

Wang, Ying; Oxer, Daniella; Hekimi, Siegfried

doi:10.1038/ncomms7393

Cited by 113 publications

(136 citation statements)

References 70 publications

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“…A recent intriguing paper supports this hypothesis. Siegfried Hekimi's laboratory has shown that controlled disruption of Coenzyme Q (CoQ) biosynthesis, through knock-out of the Mclk1 gene, severely affects mitochondrial function and dramatically reduces lifespan [38]. Interestingly, restoration of CoQ levels through administration of 2,4-dihydroxybenzoic acid (an analogue of 4-hydroxybenzoic acid, the natural precursor of CoQ) that is only able to partially rescue the mitochondrial phenotype completely rescued the shortened lifespan of Mclk1 mutant mice.…”

Section: Ros Are Not All the Samementioning

confidence: 97%

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Sanz

2016

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

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Section: Ros Are Not All the Samementioning

confidence: 97%

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Sanz

2016

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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“…Likewise, mice with a homozygous deletion of an ETC complex I subunit (Ndufs4 knockout mice) also show reduced longevity. Both of these mutant mouse models are very short‐lived and have severe respiratory and metabolic phenotypes (Kruse et al., 2008; Wang, Oxer & Hekimi, 2015). One explanation for the seemingly contradictory effects of ETC mutation and longevity is a threshold effect in which compromised mitochondrial function alters cellular function only once a critical deficiency in ATP production in reached.…”

Section: Discussionmentioning

confidence: 99%

Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice

et al. 2018

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SummaryLoss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1 −/− mice. The lack of deleterious phenotypes in Surf1 −/− mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1 −/− vs. Surf1 +/+ mice despite substantial decreases in COX activity (22%–87% across tissues). Dietary restriction (DR) increased median lifespan in both Surf1 +/+ and Surf1 −/− mice (36% and 19%, respectively). We measured gene expression, metabolites, and targeted expression of key metabolic proteins in adipose tissue, liver, and brain in Surf1 +/+ and Surf1 −/− mice. Gene expression was differentially regulated in a tissue‐specific manner. Many proteins and metabolites are downregulated in Surf1 −/− adipose tissue and reversed by DR, while in brain, most metabolites that changed were elevated in Surf1 −/− mice. Finally, mitochondrial unfolded protein response (UPRmt)‐associated proteins were not uniformly altered by age or genotype, suggesting the UPRmt is not a key player in aging or in response to reduced COX activity. While the changes in gene expression and metabolism may represent compensatory responses to mitochondrial stress, the important outcome of this study is that lifespan and healthspan are not compromised in Surf1 −/− mice, suggesting that not all mitochondrial deficiencies are a critical determinant of lifespan.

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“…The CoQ10 is 2, 3-dimethoxy-5-methyl-6-decaprenyl-1, 4-benzoquinone (Wang et al, 2015). It contains 10 isoprene units the predominant from in both mammals and birds, whereas CoQ9 (nine isoprene units) is predominant in rodents .…”

Section: Chemistry Of Coenzyme Q10mentioning

confidence: 99%

“…The CoQ10 is similar to vitamin K in its chemical structure but it is not considered a vitamin because it is synthesized in the body (Bhagavan and Chopra, 2006;Wang et al, 2015). All the fat soluble vitamins (A, D, E and K) possess isoprene units in their structures.…”

Section: Introductionmentioning

confidence: 99%

Dietary Essentiality I: Coenzyme Q10 Conditionally Essential-Review

Gopi¹,

Kumar²,

Elaiyaraja³

et al. 2015

Asian J. of Animal and Veterinary Advances

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The essentiality of nutrients keeps on changing with the advancement in nutritional research and genetic gain. The genetic gain especially in poultry sector is very high which results in increase in nutrient requirement of both the essential and non-essential nutrients. For the rapid growth the requirement of essential nutrients reaches many folds which are in direct relation with the performance, but the requirement for non-essential nutrients is an indirect one. Most of the dispensable amino acids, vitamin C, carnitine, etc. which are being synthesized endogenously are now a days unable to meet the birds requirements that warrants the dietary supply. Another important nutrient is coenzyme Q10 (CoQ10) which endogenously synthesized is now gaining much attention as a supplement for fast growing broilers. The CoQ10 can be termed as multi-functionary as each and every cell in the body needs this but quantity is being high for very active organs like heart, lungs, liver, kidney, etc. They are essential for cellular oxidative phosphorylation and regenerative antioxidant. The supplementation of CoQ10 improved the feed efficiency with reducing the electron leaks from mitochondria and increases total antioxidant capacity. For this property, CoQ10 is widely used in human medicine especially persons suffering from cardiac, neurological disorder, hypercholesterolemic condition and also even in cancer. The CoQ10 in poultry draws first attention when it is found to reducing the ascites mortality in marketable broilers. Thereafter, the advantages of CoQ10 is started to exploit with much attention to ascites, feed efficiency, cholesterol lowering effect nutraceutical and nutrigenomic property both in poultry and swine industry.

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Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis

Cited by 113 publications

References 70 publications

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Mitochondrial reactive oxygen species: Do they extend or shorten animal lifespan?

Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice

Dietary Essentiality I: Coenzyme Q10 Conditionally Essential-Review

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